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RHOC; ras homolog family member C (1p13.1)

Gene Summary

Gene:RHOC; ras homolog family member C
Aliases: H9, ARH9, ARHC, RHOH9
Location:1p13.1
Summary:This gene encodes a member of the Rho family of small GTPases, which cycle between inactive GDP-bound and active GTP-bound states and function as molecular switches in signal transduction cascades. Rho proteins promote reorganization of the actin cytoskeleton and regulate cell shape, attachment, and motility. The protein encoded by this gene is prenylated at its C-terminus, and localizes to the cytoplasm and plasma membrane. It is thought to be important in cell locomotion. Overexpression of this gene is associated with tumor cell proliferation and metastasis. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]
Databases:OMIM, VEGA, HGNC, Ensembl, GeneCard, Gene
Protein:rho-related GTP-binding protein RhoC
HPRD
Source:NCBI
Updated:14 December, 2014

Gene
Ontology:

What does this gene/protein do?
Show (38)

Cancer Overview

RhoC over-expression has been reported in ductal pancreatic adenosarcoma (Suwa, 1998) and in inflammatory breast cancers (van Golen, 1999). RhoC is also implicated in the spread of metastastic disease (Clarke, 2000).

Research Indicators

Publications Per Year (1989-2014)
Graph generated 14 December 2014 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

Tag cloud generated 14 December, 2014 using data from PubMed, MeSH and CancerIndex

Notable (6)

Scope includes mutations and abnormal protein expression.

Entity Topic PubMed Papers
Breast CancerRHOC and Breast Cancer
In an in-situ hybridization study RohC was more frequently over-expressed in inflammatory breast cancers compared with non-inflammatory breast cancers (van Golen,1999).
View Publications70
Lung CancerRHOC and Lung Cancer View Publications26
Liver CancerRHOC and Liver Cancer View Publications24
MelanomaRHOC and Melanoma View Publications15
Ovarian CancerRHOC and Ovarian Cancer View Publications9
Pancreatic CancerRHOC expression in Pancreatic Cancer View Publications8

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Related Links

Latest Publications: RHOC (cancer-related)

Zhou J, Tao Y, Peng C, et al.
miR-503 regulates metastatic function through Rho guanine nucleotide exchanger factor 19 in hepatocellular carcinoma.
J Surg Res. 2014; 188(1):129-36 [PubMed] Related Publications
BACKGROUND: Our previous work described a metastasis-related microRNAs expression profiling and revealed miR-503 regulating metastatic function in hepatocellular carcinoma (HCC) cells. Here, we investigate to define the mechanism of miR-503 regulating metastasis in HCC.
MATERIALS AND METHODS: The expressions of miR-503 in HCC cell lines and clinical tissues with different metastatic potential were investigated. Meanwhile, a metastatic human HCC cell BALB/c nude mice model was used to investigate whether miR-503 regulates metastasis of HCC in vivo. Furthermore, luciferase activity of reporter gene, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), fluorescence-activated cell sorting analysis (FACS), and invasion assay were carried out to characterize the mechanism of miR-503 regulating metastasis in HCC.
RESULTS: We confirmed the negative correlation between miR-503 expression and metastatic potential of HCC in cell lines and in clinical HCC tissues. We also showed that overexpression of miR-503 resulted in inhibition of proliferation and metastasis of HCC in vivo. Furthermore, we demonstrated that ARHGEF19 is a direct target gene of miR-503. Finally, our results indicated that ARHGEF19 overcomes the suppressive influence of miR-503 in HCC cells.
CONCLUSIONS: Our results suggest an important role of miR-503 in inhibiting metastasis of HCC through deregulating ARHGEF19.

Related: Liver Cancer


Irwin CR, Favis NA, Agopsowicz KC, et al.
Myxoma virus oncolytic efficiency can be enhanced through chemical or genetic disruption of the actin cytoskeleton.
PLoS One. 2013; 8(12):e84134 [PubMed] Free Access to Full Article Related Publications
Myxoma virus (MYXV) is one of many animal viruses that exhibit oncolytic properties in transformed human cells. Compared to orthopoxviruses like vaccinia (VACV), MYXV spreads inefficiently, which could compromise its use in treating tumors and their associated metastases. The VACV F11 protein promotes virus exit and rapid spread by inhibiting Rho signalling, which results in a disruption of cortical actin. We have previously shown that although MYXV lacks an F11 homolog, the F11L gene can be introduced into MYXV promoting the spread of this Leporipoxvirus in natural host cells. Here we show that the F11-encoding (F11L(+)) MYXV strain replicates to higher levels in a number of human cancer cells. We also show that F11L(+) MYXV induces better tumor control and prolonged survival of mice bearing MDA-MB-231 cancer cells. Furthermore, we show that this virus also spreads more efficiently from the site of growth in one injected tumor, to a second untreated tumor. While we focused mostly on the use of a modified MYXV we were able to show that the effects of F11 on MYXV growth in cancer cells could be mimicked through the use of pharmacological inhibition or siRNA-mediated silencing of key regulators of cortical actin (RhoA, RhoC, mDia1, or LIMK2). These data suggest that it may be possible to increase the oncolytic efficacy of wild-type MYXV using chemical inhibitors of RhoA/C or their downstream targets. Furthermore, since all viruses must overcome barriers to exit posed by structures like cortical actin, these findings suggest that the oncolytic activity of other viruses may be enhanced through similar strategies.

Related: Breast Cancer RHOA


Marcucci G, Yan P, Maharry K, et al.
Epigenetics meets genetics in acute myeloid leukemia: clinical impact of a novel seven-gene score.
J Clin Oncol. 2014; 32(6):548-56 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
PURPOSE: Molecular risk stratification of acute myeloid leukemia (AML) is largely based on genetic markers. However, epigenetic changes, including DNA methylation, deregulate gene expression and may also have prognostic impact. We evaluated the clinical relevance of integrating DNA methylation and genetic information in AML.
METHODS: Next-generation sequencing analysis of methylated DNA identified differentially methylated regions (DMRs) associated with prognostic mutations in older (≥ 60 years) cytogenetically normal (CN) patients with AML (n = 134). Genes with promoter DMRs and expression levels significantly associated with outcome were used to compute a prognostic gene expression weighted summary score that was tested and validated in four independent patient sets (n = 355).
RESULTS: In the training set, we identified seven genes (CD34, RHOC, SCRN1, F2RL1, FAM92A1, MIR155HG, and VWA8) with promoter DMRs and expression associated with overall survival (OS; P ≤ .001). Each gene had high DMR methylation and lower expression, which were associated with better outcome. A weighted summary expression score of the seven gene expression levels was computed. A low score was associated with a higher complete remission (CR) rate and longer disease-free survival and OS (P < .001 for all end points). This was validated in multivariable models and in two younger (< 60 years) and two older independent sets of patients with CN-AML. Considering the seven genes individually, the fewer the genes with high expression, the better the outcome. Younger and older patients with no genes or one gene with high expression had the best outcomes (CR rate, 94% and 87%, respectively; 3-year OS, 80% and 42%, respectively).
CONCLUSION: A seven-gene score encompassing epigenetic and genetic prognostic information identifies novel AML subsets that are meaningful for treatment guidance.

Related: Cytarabine Daunorubicin Acute Myeloid Leukemia (AML)


Kim H, Gao W, Ho M
Novel immunocytokine IL12-SS1 (Fv) inhibits mesothelioma tumor growth in nude mice.
PLoS One. 2013; 8(11):e81919 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Mesothelin is a glycosylphosphatidylinositol-anchored glycoprotein that is highly expressed on the cell surface of malignant mesothelioma. Monoclonal antibodies against mesothelin are being evaluated for the treatment of mesothelioma. Immunocytokines represent a novel class of armed antibodies. To provide an alternative approach to current mesothelin-targeted antibody therapies, we have developed a novel immunocytokine based on interleukin-12 (IL12) and the SS1 Fv specific for mesothelin. IL12 possesses potent anti-tumor activity in a wide variety of solid tumors. The newly-developed recombinant immunocytokine, IL12-SS1 (Fv), was produced in insect cells using a baculovirus-insect cell expression system. The SS1 single-chain Fv was fused to the C terminus of the p35 subunit of IL12 through a short linker (GSADGG). The single-chain IL12-SS1 (Fv) immunocytokine bound native mesothelin proteins on malignant mesothelioma (NCI-H226) and ovarian (OVCAR-3) cells as well as recombinant mesothelin on A431/H9 cells. The immunocytokine retained sufficient bioactivity of IL12 and significantly inhibited human malignant mesothelioma (NCI-H226) grown in the peritoneal cavity of nude mice and showed comparable anti-tumor activity to that of the SS1P immunotoxin. IL12-SS1 (Fv) is the first reported immunocytokine to mesothelin-positive tumors and may be an attractive addition to mesothelin-targeted cancer therapies.

Related: Monoclonal Antibodies Lung Cancer Mesothelioma


Malissein E, Meunier E, Lajoie-Mazenc I, et al.
RhoA and RhoC differentially modulate estrogen receptor α recruitment, transcriptional activities, and expression in breast cancer cells (MCF-7).
J Cancer Res Clin Oncol. 2013; 139(12):2079-88 [PubMed] Related Publications
PURPOSE: RhoA and RhoC are closely related, small GTPases that are clearly involved in breast cancer tumorigenesis. Nonetheless, their specific roles in the control of estrogen receptor alpha (ERα) activities have not been elucidated.
METHODS: We used siRNA sequences to specifically down-regulate RhoA and RhoC expression in ERα-positive breast adenocarcinoma MCF-7 cells. We then analyzed the consequences of down-regulation on ERα expression, ERα recruitment to the promoters of four target genes, and the mRNA levels of those genes.
RESULTS: We demonstrated that RhoA and RhoC clearly and similarly modulated ERα recruitment to the vitellogenin estrogen responsive element (ERE) present in a luciferase reporter gene and to the promoters of progesterone receptor (PR), cathepsin D, and pS2 genes. Besides, RhoA up-regulated the ERE-luciferase reporter gene activity and PR mRNA expression and tended to down-regulate cathepsin D and pS2 mRNA expression. Conversely, RhoC inhibition had no significant effect at the mRNA level. Furthermore, RhoA inhibition, and to a lesser extent RhoC inhibition, increased ERα expression. No alteration in ERα mRNA levels was observed, suggesting potential post-translational control.
CONCLUSIONS: Taken together, our results strongly suggest that RhoA and RhoC play different, but clear, roles in ERα signaling. These GTPases are definitely involved, along with RhoB, in ERα recruitment and, to some extent, ERα cofactor balance. We hypothesize a differential role of RhoA in breast cancer tumors that depend on hormone status.

Related: Breast Cancer Signal Transduction RHOA


Xue G, Zou X, Zhou JY, et al.
Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro.
Biochem Biophys Res Commun. 2013; 439(2):196-202 [PubMed] Related Publications
Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A's dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

Related: Apoptosis Stomach Cancer Gastric Cancer


Chen PC, Peng JR, Huang L, et al.
Overexpression of human telomerase reverse transcriptase promotes the motility and invasiveness of HepG2 cells in vitro.
Oncol Rep. 2013; 30(3):1157-64 [PubMed] Related Publications
Recent studies have indicated that telomerase activity promotes cancer invasion and metastasis, but the underlying mechanism remains unclear. Several studies have shown that expression of exogenous human telomerase reverse transcriptase (hTERT) can promote motility and invasiveness among telomerase-negative tumor cells, and inhibition of endogenous telomerase activity can reduce invasiveness in tumor cells. However, whether overexpression of hTERT can further enhance the motility and invasiveness of telomerase‑positive tumor cells has yet to be determined. In the present study, we showed that stable overexpression of hTERT can increase telomerase activity and telomere length, which significantly promotes the invasive and metastatic potential of telomerase‑positive HepG2 cells but does not affect cell proliferation. Further analysis suggested that enhanced invasiveness and metastasis may act through corresponding upregulation of mRNA and protein expression of matrix metalloproteinase 9 (MMP9) and Ras homolog gene family member C (RhoC). Our study indicated that exogenous expression of hTERT may promote invasiveness and metastasis through upregulation of MMP9 and RhoC.

Related: MMP9: matrix metallopeptidase 9 TERT


Zhao Y, Zheng HC, Chen S, et al.
The role of RhoC in ovarian epithelial carcinoma: a marker for carcinogenesis, progression, prognosis, and target therapy.
Gynecol Oncol. 2013; 130(3):570-8 [PubMed] Related Publications
BACKGROUND: Ras homolog gene family member C (RhoC) is a small G protein/guanosine triphosphatase involved in tumor mobility, invasion, and metastasis.
METHODS: After RhoC siRNA transfection, we measured the changes in phenotypes and some relevant molecules in ovarian carcinoma cell, OVCAR3. The mRNA and protein expression of RhoC was detected in ovarian tumors.
RESULTS: RhoC siRNA transfection resulted in low growth, G1 arrest, and apoptotic induction in the OVCAR3 in comparison with the control and mock. Following RhoC knockdown, there was reduced mRNA or protein expression of protein kinase B (Akt), signal transducer and activator of transcription 3 (stat3), bcl-xL, surviving and phosphorylated p70S6 kinase (p-p70s6k), while the converse was true for Bax and caspase-3. Lovastatin induced apoptosis, suppressed proliferation, migration and invasion, and disrupted lamellipodia formation in OVCAR3. Lovastatin exposure induced lower RhoC, bcl-2, matrix metalloproteinase-9 (MMP-9), survivin, Akt, bcl-xL, vascular endothelial growth factor (VEGF), and p-p70s6k expression in OVCAR3 compared to the control, but higher caspase-3 and Bax expression. RhoC mRNA and protein expression was significantly higher in ovarian carcinoma than in benign tumors and normal ovary tissue (p<0.05) and was positively associated with dedifferentiation, FIGO staging and p-p70s6k expression of ovarian carcinoma (p<0.05).
CONCLUSIONS: The up-regulated RhoC expression may affect ovarian carcinogenesis and should be considered a good biomarker for the differentiation and progression of ovarian carcinoma. RhoC plays an important role in apoptosis by modulating the relevant genes and the phosphorylation of downstream p70s6k.

Related: Apoptosis CASP3 MMP9: matrix metallopeptidase 9 Ovarian Cancer AKT1 VEGFA BIRC5


Nakayama I, Shibazaki M, Yashima-Abo A, et al.
Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells.
Int J Oncol. 2013; 43(1):63-71 [PubMed] Related Publications
Small and large non-coding RNAs (ncRNAs) contribute to the acquisition of aggressive tumor behavior in diverse human malignancies. Two types of ncRNAs, miRNA‑10b (miR-10b) and homemobox (HOX) transcript antisense RNA (HOTAIR), can suppress the translation of the HOXD10 gene, an mRNA encoding a transcriptional repressor that inhibits the expression of cell migration/invasion-associated genes. Using epithelial ovarian cancer cell lines and primary tumors, we investigated whether miR‑10b and/or HOTAIR can regulate the expression of HOXD10, and whether it permits gain of pro‑metastatic gene products, matrix metallopeptidase 14 (MMP14) and ras homolog family member C (RHOC). Overexpression of miR-10b induced a decrease in HOXD10 protein expression, and upregulated the migration and invasion abilities in ovarian cancer cell lines (P<0.05). In these cells, a significant increase of MMP14 and RHOC protein was observed. No significant upregulation of the HOXD10 protein was observed in cells with the treatment of HOTAIR-siRNA. Positive signals for HOXD10 and MMP14 proteins were observed in 47 (69%) and 25 (37%) of 68 patients with epithelial ovarian cancers. An inverse correlation between HOXD10 and MMP14 immunoreactivities was observed (P<0.05), and miR-10b expression was also inversely correlated with HOXD10 protein expression (P<0.05). These results suggested that downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells.

Related: Ovarian Cancer


Sánchez-Miguel DS, García-Dolores F, Rosa Flores-Márquez M, et al.
TRESK potassium channel in human T lymphoblasts.
Biochem Biophys Res Commun. 2013; 434(2):273-9 [PubMed] Related Publications
TRESK (TWIK-related spinal cord K(+)) channel, encoded by KCNK18 gene, belongs to the double-pore domain K(+) channel family and in normal conditions is expressed predominantly in the central nervous system. In our previous patch-clamp study on Jurkat T lymphoblasts we have characterized highly selective K(+) channel with pharmacological profile identical to TRESK. In the present work, the presence of KCNK18 mRNA was confirmed in T lymphoblastic cell lines (Jurkat, JCaM, H9) but not in resting peripheral blood lymphocytes of healthy donors. Positive immunostaining for TRESK was demonstrated in lymphoblastic cell lines, in germinal centers of non-tumoral lymph nodes, and in clinical samples of T acute lymphoblastic leukemias/lymphomas. Besides detection in the plasma membrane, intracellular TRESK localization was also revealed. Possible involvement of TRESK channel in lymphocyte proliferation and tumorigenesis is discussed.


Ridley AJ
RhoA, RhoB and RhoC have different roles in cancer cell migration.
J Microsc. 2013; 251(3):242-9 [PubMed] Related Publications
Rho GTPases are well known to regulate cell motility through activation of a variety of downstream effector proteins, including enzymes, adaptor proteins and actin nucleators. The three closely related Rho GTPases RhoA, RhoB and RhoC all have the potential to interact with the same downstream effectors, yet they have substantially different effects on cell shape and migratory properties. Here I review the different ways in which RhoA, RhoB and RhoC expression is regulated in cancer and how they play distinct roles in cancer progression. I describe their main effectors known to contribute to cell motility. Recent results from our laboratory and others indicate that RhoA, RhoB and RhoC can be activated by specific stimuli and act through different effectors to control distinct aspects of cancer cell migration and invasion. This suggests that they each make unique contributions to cancer by participating in different protein complexes.

Related: Cancer Prevention and Risk Reduction RHOA RHOB


Yau WL, Lam CS, Ng L, et al.
Over-expression of miR-106b promotes cell migration and metastasis in hepatocellular carcinoma by activating epithelial-mesenchymal transition process.
PLoS One. 2013; 8(3):e57882 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Hepatocellular carcinoma (HCC) is one the the most fatal cancers worldwide. The poor prognosis of HCC is mainly due to the developement of distance metastasis. To investigate the mechanism of metastasis in HCC, an orthotopic HCC metastasis animal model was established. Two sets of primary liver tumor cell lines and corresponding lung metastasis cell lines were generated. In vitro functional analysis demonstrated that the metastatic cell line had higher invasion and migration ability when compared with the primary liver tumor cell line. These cell lines were subjected to microRNA (miRNAs) microarray analysis to identify differentially expressed miRNAs which were associated with the developement of metastasis in vivo. Fifteen human miRNAs, including miR-106b, were differentially expressed in 2 metastatic cell lines compared with the primary tumor cell lines. The clinical significance of miR-106b in 99 HCC clinical samples was studied. The results demonstrated that miR-106b was over-expressed in HCC tumor tissue compared with adjacent non-tumor tissue (p = 0.0005), and overexpression of miR-106b was signficantly correlated with higher tumor grade (p = 0.018). Further functional studies demonstrated that miR-106b could promote cell migration and stress fiber formation by over-expressing RhoGTPases, RhoA and RhoC. In vivo functional studies also showed that over-expression of miR-106b promoted HCC metastasis. These effects were related to the activation of the epithelial-mesenchymal transition (EMT) process. Our results suggested that miR-106b expression contributed to HCC metastasis by activating the EMT process promoting cell migration in vitro and metastasis in vivo.

Related: Liver Cancer miR-21


Wang Q, Tang H, Yin S, Dong C
Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9.
Oncol Rep. 2013; 29(5):2046-52 [PubMed] Related Publications
microRNAs (miRs) play an important role in tumor initiation and progression in many types of cancer, including cholangiocarcinoma (CC). miR-138 dysregulation is frequently observed in a variety of tumors. In the present study, miR-138 was found to be downregulated in CC tissues by quantitative real-time RT-PCR. Furthermore, its potential target molecule, Ras homolog gene family, member C (RhoC) protein, was found to be highly expressed in CC tissues examined by western blot analysis. Luciferase reporter assay further demonstrated that miR-138 directly targeted RhoC. We found that the introduction of miR-138 mimics to RBE and QBC939 CC cells could reduced RhoC mRNA and protein expression, and suppressed the proliferation, G1/S transition, migration and invasion of CC cells. However, transfection with a miR-138 inhibitor induced an inverse effect in CC cells. The expression of phosphorylated extracellular signal-regulated kinase (p-ERK), matrix metalloproteinase (MMP)-2 and MMP-9 decreased following transfection with miR-138, and increased following transfection with miR-138 inhibitor in CC cells. In conclusion, RhoC upregulation induced by miR-138 downregulation promotes the malignant progression of CC cells and the underlying mechanisms of this effect involve the increase in the expression of p-ERK/MMP-2/MMP-9. Consequently, miR-138/RhoC is a potential target for the clinical diagnosis and treatment of CC.

Related: MMP2 MMP9: matrix metallopeptidase 9


Xie S, Zhu M, Lv G, et al.
Overexpression of Ras homologous C (RhoC) induces malignant transformation of hepatocytes in vitro and in nude mouse xenografts.
PLoS One. 2013; 8(1):e54493 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Ras homologous C (RhoC) is expressed in various cancers, including hepatocellular carcinoma (HCC). In this study, we first analyzed RhoC expression in 46 HCC tissue specimens and found that RhoC expression was significantly increased in HCC tissues compared to the adjacent normal liver tissues. Next, we investigated the role of RhoC in malignant transformation of normal hepatocytes. The HL7702 cell line was stably transfected with a RhoC expression vector and then subjected to cell proliferation, differentiation, colony formation, migration and invasion assays, as well as nude mouse xenograft assays. Gene expressions in these cells were determined using RT-PCR and Western blot. Overexpression of RhoC significantly promoted proliferation and anchorage-independent growth of HL7702 cells, but suppressed cell differentiation, as compared with the parental cells and the empty vector-transfected control cells. Moreover, RhoC overexpression induced migration and invasion of HL7702 cells in vitro. Molecularly, RhoC increased the expression of cell cycle-related genes, matrix metalloprotease 2 (MMP2), MMP9 and vascular endothelial growth factor (VEGF). In addition, RhoC-transfected cells formed tumors in nude mice, whereas vector-transfected HL7702 cells did not form any tumors in nude mice. This study demonstrated the role of RhoC overexpression in malignant transformation of normal human hepatocytes, suggesting that RhoC may function as an oncogene in hepatocytes.

Related: Liver Cancer


Tripathi V, Popescu NC, Zimonjic DB
DLC1 induces expression of E-cadherin in prostate cancer cells through Rho pathway and suppresses invasion.
Oncogene. 2014; 33(6):724-33 [PubMed] Related Publications
E-cadherin is a cell-cell adhesion molecule that acts as a suppressor of cancer cell invasion and its expression is downregulated in many advanced, poorly differentiated, human cancers. In this study, we found that the expression of DLC1 (deleted in liver cancer 1) tumor-suppressor gene in metastatic prostate carcinoma (PCA) cells increased the expression of E-cadherin and resulted in an elevated rate of cell-cell aggregation as measured by aggregation assay. DLC1-mediated increase in E-cadherin expression was not dependent on α-catenin, a DLC1-binding protein associated with E-cadherin, and/or cellular density. The increase of E-cadherin expression occurred at mRNA level and relied on DLC1 RhoGAP function, leading to suppression of high level of RhoA-GTP and RhoC-GTP activity in metastatic PCA cells. Application of Rho/ROCK inhibitors produced the same effect as introduction of DLC1. Knocking down of RhoA produced a moderate increase in E-cadherin whereas knocking down of RhoC resulted in a significant increase of E-cadherin. Downregulation of E-cadherin caused by constitutively active RhoA(V14) and RhoC(V14) could not be reversed by expression of DLC1 in DLC1-negative cell line. DLC1-mediated suppression of metastatic PCA cells invasion was comparable with the one associated with ectopic E-cadherin expression, or caused by suppression of Rho pathway either by Rho/ROCK inhibitors, or by shRNA repression. This study demonstrates that DLC1 expression positively regulates E-cadherin and suppresses highly metastatic PCA cell invasion by modulating Rho pathway, which appears as a feasible therapeutic target in cancers with high activity of RhoGTPases.

Related: Prostate Cancer


Korkina O, Dong Z, Marullo A, et al.
The MLK-related kinase (MRK) is a novel RhoC effector that mediates lysophosphatidic acid (LPA)-stimulated tumor cell invasion.
J Biol Chem. 2013; 288(8):5364-73 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
The small GTPase RhoC is overexpressed in many invasive tumors and is essential for metastasis. Despite its high structural homology to RhoA, RhoC appears to perform functions that are different from those controlled by RhoA. The identity of the signaling components that are differentially regulated by these two GTPases is only beginning to emerge. Here, we show that the MAP3K protein MRK directly binds to the GTP-bound forms of both RhoA and RhoC in vitro. However, siRNA-mediated depletion of MRK in cells phenocopies depletion of RhoC, rather than that of RhoA. MRK depletion, like that of RhoC, inhibits LPA-stimulated cell invasion, while depletion of RhoA increases invasion. We also show that active MRK enhances LPA-stimulated invasion, further supporting a role for MRK in the regulation of invasion. Depletion of either RhoC or MRK causes sustained myosin light chain phosphorylation after LPA stimulation. In addition, activation of MRK causes a reduction in myosin light chain phosphorylation. In contrast, as expected, depletion of RhoA inhibits myosin light chain phosphorylation. We also present evidence that both RhoC and MRK are required for LPA-induced stimulation of the p38 and ERK MAP kinases. In conclusion, we have identified MRK as a novel RhoC effector that controls LPA-stimulated cell invasion at least in part by regulating myosin dynamics, ERK and p38.

Related: Cancer Prevention and Risk Reduction Ovarian Cancer Signal Transduction RHOA


Lv J, Xiao Q, Wang L, et al.
Fucoidan prevents multiple myeloma cell escape from chemotherapy-induced drug cytotoxicity.
Fitoterapia. 2013; 84:257-63 [PubMed] Related Publications
Minimal residual disease (MRD) occurrence with some chemotherapy drugs that promote tumor cell escape is also a key factor in blood malignancy relapse. We observed that cytarabine promotes multiple myeloma (MM) cell escape and that the number of cells in the lower chamber increased with increasing clinical disease stage in in vitro model which was constructed by a Boyden chamber, matrigel glue and serum from MM patients in different disease stages. The mechanism of cytarabine that promotes MM cell escape is closely associated with the up-regulation of CXCR4. SDF-1α can up-regulate the expression of MMP9 and RHoC proteins in MM cells with up-regulated CXCR4, and further promote the cell escape. Fucoidan, a sulfated polysaccharide in the cell wall matrix of brown algae, has attracted much attention for its multiple biological activities, and we further explored the effects and possible underlying mechanisms of fucoidan on MM cell escape from cytarabine cytotoxicity. The results show that fucoidan may decrease MM cell escape from cytarabine cytotoxicity, and that fucoidan can down-regulate CXCR4, MMP9 and RHoC expression. This research provides new direction for investigating MRD occurrence and prevention.

Related: Apoptosis Cytarabine Myeloma Myeloma - Molecular Biology


Lazarini M, Traina F, Machado-Neto JA, et al.
ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells.
Biochim Biophys Acta. 2013; 1832(2):365-74 [PubMed] Related Publications
BACKGROUND: Several Rho GTPase-activating proteins (RhoGAPs) are implicated in tumor progression through their effects on Rho GTPase activity. ARHGAP21 is a RhoGAP with increased expression in head and neck squamous cell carcinoma and with a possible role in glioblastoma tumor progression, yet little is known about the function of ARHGAP21 in cancer cells. Here we studied the role of ARHGAP21 in two prostate adenocarcinoma cell lines, LNCaP and PC3, which respectively represent initial and advanced stages of prostate carcinogenesis.
RESULTS: ARHGAP21 is located in the nucleus and cytoplasm of both cell lines and its depletion resulted in decreased proliferation and increased migration of PC3 cells but not LNCaP cells. In PC3 cells, ARHGAP21 presented GAP activity for RhoA and RhoC and induced changes in cell morphology. Moreover, its silencing altered the expression of genes involved in cell proliferation and cytoskeleton organization, as well as the endothelin-1 canonical pathway.
CONCLUSIONS: Our results reveal new functions and signaling pathways regulated by ARHGAP21, and indicate that it could contribute to prostate cancer progression.

Related: Prostate Cancer


Zhang Z, Chen X, Chang X, et al.
Vaccination with embryonic stem cells generates effective antitumor immunity against ovarian cancer.
Int J Mol Med. 2013; 31(1):147-53 [PubMed] Related Publications
To date, only a few studies have suggested that human embryonic stem cells (hESCs) might effectively immunize against colon and lung cancer. The purpose of this study was to investigate the therapeutic potential of hESCs as a vaccine to induce widespread antitumor effects in different animal models and various types of cancer. C57BL/6 mice with ID8 ovarian cancer cell and Fischer 344 rats with NuTu-19 ovarian cancer cell models were used. Fifty-four mice were divided into six groups with nine mice in each group. Each mouse was immunized with pre-inactivated hESCs (H9) or mouse embryonic stem cells (mESCs; IVP-ES1) or ID8 or phosphate-buffered saline (PBS). Twenty-four rats were divided into four groups with six rats in each group, each rat immunized with pre-inactivated hESCs (H9) or NuTu-19 or PBS. After the vaccination, each mouse was challenged with live ID8 cells subcutaneously, and each rat was challenged with live NuTu-19 cells intraperitoneally. We discovered that vaccination of mice with the hESC line H9 and the mESC line IVP-ES1 generated consistent cellular and humoral immune responses against ID8 ovarian cancer. H9 and IVP-ES1 vaccinated mice obtained antitumor immune protection, and H9 vaccinated rats had the longest survival time and least distant metastases. No evidence of side-effects was observed. We also compared the immunogenicity against ovarian cancer between the hESC line, H9, and the mESC line, IVP-ES1, that derived from the inner cell mass in different species. We found that there were no significant differences between them. Furthermore, immunohistochemical staining revealed that several oncogenes and tumor suppressor genes, such as HER-2, C-myc, p53, and nm23, were expressed in H9, many of which were also shared by ovarian cancer. hESC vaccines can induce antitumor effects in two animal models and in ovarian cancer, indicating that the activity of the vaccine is universal, and, more importantly, it is safe.

Related: ERBB2 (HER2) Ovarian Cancer TP53


Zhang ZJ, Chen XH, Chang XH, et al.
Human embryonic stem cells--a potential vaccine for ovarian cancer.
Asian Pac J Cancer Prev. 2012; 13(9):4295-300 [PubMed] Related Publications
OBJECTIVE: To investigate the therapeutic potential of human embryonic stem cells (hESCs) as a vaccine to induce an immune response and provide antitumor protection in a rat model.
METHODS: Cross-reactivity of antigens between hESCs and tumour cells was screened by immunohistochemistry. Fischer 344 rats were divided into 7 groups, with 6 rats in each, immunized with: Group 1, hESC; Group 2, pre-inactivated mitotic NuTu-19; Group 3 PBS; Group 4, hESC; Group 5, pre-inactivated mitotic NuTu-19; Group 6, PBS; Group 7, hESC only. At 1 (Groups 1-3) or 4 weeks (Groups 4-6) after the last vaccination, each rat was challenged intraperitoneally with NuTu-19. Tumor growth and animal survival were closely monitored. Rats immunized with H9 and NuTu- 19 were tested by Western blot analysis of rat orbital venous blood for cytokines produced by Th1 and Th2 cells.
RESULTS: hESCs presented tumour antigens, markers, and genes related to tumour growth, metastasis, and signal pathway interactions. The vaccine administered to rats in Group 1 led to significant antitumor responses and enhanced tumor rejection in rats with intraperitoneal inoculation of NuTu-19 cells compared to control groups. In contrast, rats in Group 4 did not display any elevation of antitumour responses. Western blot analysis found cross-reactivity among antibodies generated between H9 and NuTu-19. However, the cytokines did not show significant differences, and no side effects were detected.
CONCLUSION: hESC-based vaccination is a promising modality for immunotherapy of ovarian cancer.

Related: Ovarian Cancer


Wu Y, Tao Y, Chen Y, Xu W
RhoC regulates the proliferation of gastric cancer cells through interaction with IQGAP1.
PLoS One. 2012; 7(11):e48917 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Our previous research results showed that both Ras homolog family member C (RhoC) and IQ-domain GTPase-activating protein 1 (IQGAP1) were over-expressed in gastric cancer tissues and cells, but their role in tumorigenensis has not been addressed clearly. Herein we reported the proliferation stimulating effect of RhoC and IQGAP1 on gastric cancer cells and the interaction between two proteins in regulating the proliferation of gastric cancer cells. Plasmids and viral constructs encoding target siRNA and DNA were used to alter the expression of RhoC and IQGAP1. MTT method and BrdU incorporation assay were used for analyzing the effect of RhoC and different structures of IQGAP1 on proliferation. Protein levels of IQGAP1 and RhoC in cell lines were detected by Western blotting. Immunofluorescence and Co-Immunoprecipitation assays were applied to investigate the localization and binding between RhoC and IQGAP1. The results showed that RhoC, IQGAP1 and the C-terminal fragment of IQGAP1 significantly stimulated the proliferation of gastric cancer cells, and enhanced the expression of cyclin E and cyclin D1. By contrast, reduction of endogenous IQGAP1 or RhoC by siRNA attenuated cell proliferation. The depletion of IQGAP1 expression by siRNA significantly blocked the proliferative activity of constitutively active RhoC, while RhoC silencing by siRNA had no effect on IQGAP1-induced proliferation in gastric cancer cells. Co-immunoprecipitation and Immunofluorescence assays showed that RhoC and IQGAP1 bound each other. In conclusion, our results suggest that RhoC stimulates the proliferation of gastric cancer cells through recruiting IQGAP1 as an effector.

Related: Stomach Cancer Gastric Cancer


Lehman HL, Dashner EJ, Lucey M, et al.
Modeling and characterization of inflammatory breast cancer emboli grown in vitro.
Int J Cancer. 2013; 132(10):2283-94 [PubMed] Related Publications
Inflammatory breast cancer (IBC) is the deadliest form of breast cancer, presenting as intralymphatic emboli. Emboli within the dermal lymphatic vessels are thought to contribute to rapid metastasis. The lack of appropriate in vitro models has made it difficult to accurately study how IBC emboli metastasize. To date, attempts at creating IBC tumor emboli in vitro have used 3D culture on a solid layer of Matrigel(TM) , which does not resemble the physical properties of the lymphatic system. Dermal lymphatic fluid produces oscillatory fluid shear forces and is 1.5-1.7-fold more viscous than water with a pH range of 7.5-7.7. We have established a method for forming tumor emboli by culturing the IBC cell lines in suspension with either polyethylene glycol- or hyaluronic acid-containing medium and oscillatory fluid shear forces. Non-IBC cells do not form emboli under identical conditions. In vitro IBC emboli were analyzed for expression of markers associated with patient emboli and their ability to undergo invasion. In a direct comparison, the in vitro IBC emboli closely resemble IBC patient emboli with respect to size, composition and E-cadherin expression. Further, cells from the emboli are able to invade in clusters via RhoC GTPase-dependent amoeboid movement. Invasion by clusters of IBC cells is disrupted by exposure to TGFβ. This study provides a biologically relevant in vitro model to accurately grow and study inflammatory breast cancer biology and metastasis.

Related: Signal Transduction


Majid S, Dar AA, Saini S, et al.
MicroRNA-1280 inhibits invasion and metastasis by targeting ROCK1 in bladder cancer.
PLoS One. 2012; 7(10):e46743 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
MicroRNAs (miRNAs) are non-protein-coding sequences that can function as oncogenes or tumor suppressor genes. This study documents the tumor suppressor role of miR-1280 in bladder cancer. Quantitative real-time PCR and in situ hybridization analyses showed that miR-1280 is significantly down-regulated in bladder cancer cell lines and tumors compared to a non-malignant cell line or normal tissue samples. To decipher the functional significance of miR-1280 in bladder cancer, we ectopically over-expressed miR-1280 in bladder cancer cell lines. Over-expression of miR-1280 had antiproliferative effects and impaired colony formation of bladder cancer cell lines. FACS (fluorescence activated cell sorting) analysis revealed that re-expression of miR-1280 in bladder cancer cells induced G2-M cell cycle arrest and apoptosis. Our results demonstrate that miR-1280 inhibited migration and invasion of bladder cancer cell lines. miR-1280 also attenuated ROCK1 and RhoC protein expression. Luciferase reporter assays demonstrated that oncogene ROCK1 is a direct target of miR-1280 in bladder cancer. This study also indicates that miR-1280 may be of diagnostic and prognostic importance in bladder cancer. For instance, ROC analysis showed that miR-1280 expression can distinguish between malignant and normal bladder cancer cases and Kaplan-Meier analysis revealed that patients with miR-1280 high expression had higher overall survival compared to those with low miR-1280 expression. In conclusion, this is the first study to document that miR-1280 functions as a tumor suppressor by targeting oncogene ROCK1 to invasion/migration and metastasis. Various compounds are currently being used as ROCK1 inhibitors; therefore restoration of tumor suppressor miR-1280 might be therapeutically useful either alone or in combination with these compounds in the treatment of bladder cancer.

Related: Apoptosis Bladder Cancer Bladder Cancer - Molecular Biology


Willmer T, Contu L, Blatch GL, Edkins AL
Knockdown of Hop downregulates RhoC expression, and decreases pseudopodia formation and migration in cancer cell lines.
Cancer Lett. 2013; 328(2):252-60 [PubMed] Related Publications
The Hsp90/Hsp70 organising protein (Hop) is a co-chaperone that mediates the interaction of Hsp90 and Hsp70 molecular chaperones during assembly of Hsp90 complexes in cells. Formation of Hsp90 complexes is a key intermediate step in the maturation and homeostasis of oncoproteins and several hormone receptors. In this paper, we demonstrate that knockdown of Hop decreased migration of Hs578T and MDA-MB-231 breast cancer cells. Hop was identified in isolated pseudopodia fractions; it colocalised with actin in lamellipodia, and co-sedimented with purified actin in vitro. Knockdown of Hop caused a decrease in the level of RhoC GTPase, and significantly inhibited pseudopodia formation in Hs578T cells. Our data suggest that Hop regulates directional cell migration by multiple unknown mechanisms.

Related: Cancer Prevention and Risk Reduction


Vigil D, Kim TY, Plachco A, et al.
ROCK1 and ROCK2 are required for non-small cell lung cancer anchorage-independent growth and invasion.
Cancer Res. 2012; 72(20):5338-47 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Evidence is emerging that the closely related ROCK1 and ROCK2 serine/threonine kinases support the invasive and metastatic growth of a spectrum of human cancer types. Therefore, inhibitors of ROCK are under preclinical development. However, a key step in their development involves the identification of genetic biomarkers that will predict ROCK inhibitor antitumor activity. One identified mechanism for ROCK activation in cancer involves the loss of function of the DLC1 tumor suppressor gene, which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases. DLC-1 loss may lead to hyperactivation of RhoA/C and its downstream effectors, the ROCK kinases. We therefore determined whether loss of DLC-1 protein expression identifies non-small cell lung carcinoma (NSCLC) cell lines whose growth and invasion phenotypes are sensitive to ROCK inhibition. We identified and characterized a novel small molecule pharmacologic inhibitor of ROCK and additionally applied genetic approaches to impair ROCK1 and/or ROCK2 activity, and we determined that although NSCLC anchorage-dependent growth was ROCK-independent, both anchorage-independent growth and Matrigel invasion were ROCK-dependent. However, loss of DLC-1 expression did not correlate with ROCK activation or with OXA-06 sensitivity. Unexpectedly, suppression of ROCK1 or ROCK2 expression alone was sufficient to impair anchorage-independent growth, supporting their nonoverlapping roles in oncogenesis. Mechanistically, the block in anchorage-independent growth was associated with accumulation of cells in the G(0)-G(1) phase of the cell cycle, but not increased anoikis. We conclude that ROCK may be a useful therapeutic target for NSCLC.

Related: Non-Small Cell Lung Cancer Lung Cancer


Hurley PJ, Marchionni L, Simons BW, et al.
Secreted protein, acidic and rich in cysteine-like 1 (SPARCL1) is down regulated in aggressive prostate cancers and is prognostic for poor clinical outcome.
Proc Natl Acad Sci U S A. 2012; 109(37):14977-82 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.

Related: Prostate Cancer


Rosenthal DT, Zhang J, Bao L, et al.
RhoC impacts the metastatic potential and abundance of breast cancer stem cells.
PLoS One. 2012; 7(7):e40979 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
Cancer stem cells (CSCs) have been shown to promote tumorigenesis of many tumor types, including breast, although their relevance to cancer metastasis remains unclear. While subpopulations of CSCs required for metastasis have been identified, to date there are no known molecular regulators of breast CSC (BCSC) metastasis. Here we identify RhoC GTPase as an important regulator of BCSC metastasis, and present evidence suggesting that RhoC also modulates the frequency of BCSCs within a population. Using an orthotopic xenograft model of spontaneous metastasis we discover that RhoC is both necessary and sufficient to promote SUM149 and MCF-10A BCSC metastasis--often independent from primary tumor formation--and can even induce metastasis of non-BCSCs within these cell lines. The relationship between RhoC and BCSCs persists in breast cancer patients, as expression of RhoC and the BCSC marker ALDH1 are highly correlated in clinical specimens. These results suggest new avenues to combating the deadliest cells driving the most lethal stage of breast cancer progression.

Related: Breast Cancer


Zaravinos A, Volanis D, Lambrou GI, et al.
Role of the angiogenic components, VEGFA, FGF2, OPN and RHOC, in urothelial cell carcinoma of the urinary bladder.
Oncol Rep. 2012; 28(4):1159-66 [PubMed] Article available free on PMC after 20/02/2015 Related Publications
The objective of this study was to analyze the expression profile of the angiogenic components, vascular endothelial growth factor-A (VEGFA), basic fibroblast growth factor-2 (FGF2), osteopontin (OPN) and ras homolog gene family, member C (RHOC), in urothelial cell carcinoma (UCC) of the urinary bladder and to examine their role as candidate diagnostic biomarkers. Using qPCR, 77 samples of UCC of the urinary bladder and 77 matched tumor-associated normal samples were investigated to determine the expression of the four angiogenic components. The correlation between gene expression, patient survival and pathological features of the tumors was also examined. The VEGFA and OPN transcript levels were greater in the bladder cancer tissue than in the normal urothelium (P<0.001). Patients with higher VEGFA mRNA levels showed a tendency towards shorter cancer-specific survival. OPN levels showed a gradual increase, the lowest levels being found in non-invasive carcinoma and the highest in muscle invasive tumors. Elevated OPN levels indicated poor prognosis in connection with advanced disease stage (P<0.001). Both superficially invasive and muscle invasive tumors had significantly higher FGF2 levels compared to the control tissues (P=0.018 and P=0.050, respectively). Moreover, FGF2 was significantly higher in the metastatic vs. the non-metastatic tumors (P=0.0097). FGF2 levels exhibited a trend towards a correlation with worse patient survival. RHOC mRNA levels were higher in muscle invasive compared to superficially invasive tumors, as well as in grade III vs. grade I/II tumors. Furthermore, we detected worse overall survival for patients with high RHOC expression levels. VEGFA and FGF2 exhibited the best linear combination in the ROC curves for specificity and sensitivity. Thus, VEGFA and FGF2 may serve as candidate biomarkers for diagnostic purposes. Higher OPN expression may be used as a potential biomarker to predict patient survival relative to advanced tumor stage. However, further studies are required to investigate its role in urinary bladder carcinogenesis.

Related: FGF2 Bladder Cancer Bladder Cancer - Molecular Biology VEGFA


Dong CG, Wu WK, Feng SY, et al.
Co-inhibition of microRNA-10b and microRNA-21 exerts synergistic inhibition on the proliferation and invasion of human glioma cells.
Int J Oncol. 2012; 41(3):1005-12 [PubMed] Related Publications
MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene regulators. Alterations in the expression of miRNAs have been implicated in the pathogenesis and development of most human malignancies. Recent data indicate that microRNA-21 and microRNA-10b are significantly elevated in glioblastoma multiforme (GBM) suggesting their role in the regulation of multiple genes associated with cancer. In this study, U87MG human glioblastoma cells were treated with miRNA inhibitors targeting miR-10b and miR-21, alone or in combination. The results showed that the miR-21 inhibitor additively interacted with miR-10b inhibitor on U87MG cells. The 50% inhibitory concentration values were dramatically decreased in cells treated with the combination of miR-10b and miR-21 inhibitors. Furthermore, inhibitors synergistically combined, enhanced apoptosis significantly and reduced invasion ability assessed by flow cytometry and Transwell migration assay. Thus, the miR-21 inhibitor may interrupt the activity of EGFR pathways, increasing PDCD4 and TPM1 expression and reducing MMP activities, independently of PTEN status. Meanwhile, miR-10b inhibitor reduced by Twist proceeds to inhibit translation of the mRNA encoding HOXD10 leading to the increase of the expression of the well-characterized pro-metastatic gene RHOC. Taken together, these data strongly suggest that a combination of miR-21 inhibitor and miR-10b inhibitor could be an effective therapeutic strategy for controlling the growth of GBM by inhibiting oncogene expression and overexpressing tumor suppressor genes. Moreover, a regulatory strategy based on the combination of miRNA inhibitors may provide insights into the mechanisms of the modulation of signaling genes involved in tumor cell apoptosis and invasiveness.

Related: Apoptosis PTEN Signal Transduction miR-21 PDCD4


Tian Y, Liu Y, Qu J, et al.
HBV regulated RhoC expression in HepG2.2.15 cells by enhancing its promoter activity.
J Basic Microbiol. 2013; 53(5):461-8 [PubMed] Related Publications
Many studies showed that RhoC-GTPases are central molecules in oncogenic transformation. The expression of RhoC is significantly increased in hepatocellular carcinoma (HCC). HBV is the major risk factor for HCC. However, it is unknown whether HBV regulating RhoC expression. In this study, we showed the RhoC expression was significantly higher in HepG2.2.15 than that in HepG2 cells. HBV could up-regulate RhoC expression through enhancing the activity of its promoter, and HBs and HBx may involve in this process. After silencing HBs and HBx expressions by using RNA interference, the expression of RhoC in HepG2.2.15 cells could be obviously inhibited. These results would provide useful information for understanding mechanism of HCC induced by HBV infection.

Related: Liver Cancer


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