Research IndicatorsGraph generated 15 March 2017 using data from PubMed using criteria.
Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic. Tag cloud generated 15 March, 2017 using data from PubMed, MeSH and CancerIndex
Specific Cancers (5)
Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.
Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).
Numbers shown below represent number of publications held in OncomiRDB database for Oncogenic and Tumor-Suppressive MicroRNAs.
|Tissue||Target Gene(s)||Regulator(s)||MIR106B Function in Cancer||Effect|
-prostate cancer (3)
|increase cell adhesion (1)|
promote cell growth (1)
override radiation-induced cell cycle G2/M arrest (1)
override radiation-induced cell growth inhibition (1)
-hepatocellular carcinoma (2)
|induce cell proliferation (1)|
induce anchorage-independent cell growth (1)
promote cell cycle G1/S transition (1)
promote cell proliferation (1)
-Hodgkin's lymphoma (1)
-chronic lymphocytic leukemia (1)
|promote cell cycle progression (1)||oncogenic
-breast cancer (1)
-colon cancer (1)
|CDKN1A (1)||promote cell proliferation (1)||oncogenic
|MCM7_intron (1)||inhibit cell proliferation (1)||tumor-suppressive
-gastric cancer (1)
|CDKN1A (1)||increase cell cycle G1/S transition (1)||oncogenic
|head and neck (1)|
-laryngeal carcinoma (1)
|RB1 (1)||reduce cell cycle G0/G1 arrest (1)||oncogenic
Source: OncomiRDB Wang D. et al. Bioinformatics 2014, 30(15):2237-2238.
miRBase, University of Manchester
Annotated database entry including the location and sequence of the mature miRNA sequence.
miRCancer, East Carolina University
Search miRCancer for miR-106b associations with cancer and associated genes.
OMIM, Johns Hopkin University
Referenced article focusing on the relationship between phenotype and genotype.
International Cancer Genome Consortium.
Summary of gene and mutations by cancer type from ICGC
COSMIC, Sanger Institute
Somatic mutation information and related details
GEO Profiles, NCBI
Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository.
Latest Publications: MIR106B (cancer-related)
Dai F, Liu T, Zheng S, et al.MiR-106b promotes migration and invasion through enhancing EMT via downregulation of Smad 7 in Kazakh's esophageal squamous cell carcinoma.
Tumour Biol. 2016; 37(11):14595-14604 [PubMed
] Related Publications
Accumulated evidence suggests that miR-106b played a key role in the promotion of the metastases of cancer; however, little is known about miR-106b in esophageal squamous cell carcinoma (ESCC). To investigate expression level of miR-106b in ESCC tissues, quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect miR-106b expression in 35 Kazakh's ESCC and paired normal adjacent tissues (NATs). To evaluate the role mediated by miR-106b in the proliferation, migration, and invasion, MTT, wound healing, and transwell assays were employed, respectively. Luciferase reporter assay was used to identify the downstream target through miR-106b. To understand the regulation between miR-106b and Smad 7, qRT-PCR and western blot were performed. The present study showed that miR-106b was pronouncedly upregulated in ESCC relative to paired NAT and that upregulated miR-106b was significantly associated with lymph node metastases. MiR-106b was found to be able to promote proliferation, migration, and invasion of ESCC cells in vitro. Smad 7 was confirmed as a downstream target of miR-106b in our experimental setting. Smad 7 was remarkably downregulated in ESCC compared with paired NAT. In addition, upregulation of miR-106b can promote epithelial mesenchymal transition (EMT) in ESCC cell in vitro. Our results indicated that miR-106b can promote migration and invasion of ESCC cells through enhancing EMT process via downregulation of Smad 7, suggesting that miR-106b can be a potential molecular phenotype in ESCC metastases.
Majeed W, Iftikhar A, Khaliq T, et al.Gastric Carcinoma: Recent Trends in Diagnostic Biomarkers and Molecular Targeted Therapies.
Asian Pac J Cancer Prev. 2016; 17(7):3053-60 [PubMed
] Related Publications
Gastric cancer is generally associated with poor survival rates and accounts for a remarkable proportion of global cancer mortality. The prevalence of gastric carcinoma varies in different regions of world and across teh various ethnic groups. On the basis of pathological assessment, gastric cancer can be categorized as intestinal and diffuse carcinomas. The etiology is diverse, including chemical carcinogen exposure, and high salt intake Helicobacter pylori also plays a vital role in the pathogenesis of certain gastric carcinomas. The development of gastric cancer involves various alterations in mRNAs, genes (GOLPH3, MTA2) and proteins (Coronins). miRNAs, Hsamir135b, MiR21, miR106b, miR17, miR18a, MiR21, miR106b, miR17, miR18a and MiRNA375, miRNA1955p are the latest diagnostic biomarkers which can facilitate the early diagnosis of gastric carcinomas. Recent development in the treatment strategies for gastric carcinoma include the introduction of monoclonal antibodies, TKI inhibitors, inhibitors of PDGFR β, VEGFR1, VEGFR2, AntiEGFR and antiHER2 agents which can be applied along with conventional therapies.
Zhou K, Zhang T, Fan Y, et al.MicroRNA-106b promotes pituitary tumor cell proliferation and invasion through PI3K/AKT signaling pathway by targeting PTEN.
Tumour Biol. 2016; 37(10):13469-13477 [PubMed
] Related Publications
The purpose of this study was to investigate the expression of microRNA-106b (miR-106b) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in pituitary tumor and to confirm whether miR-106b promotes proliferation and invasion of pituitary tumor cells through the PI3K/AKT signaling pathway by targeted regulation of PTEN expression, and thereby to find new targets for the treatment of pituitary tumor. Fifty-five cases of pituitary tumor tissue samples were collected, including 29 cases of invasive pituitary tumor, non-invasive 26 cases, and 8 normal pituitaries. The expression level of miR-106b in pituitary tumor tissue was detected by quantitative real-time PCR, and the expression of PTEN protein was detected by immunohistochemistry. PTEN 3'-untranslated region (UTR) luciferase vector was constructed, and dual-luciferase reporter gene assay was employed to examine the effect of miR-106b on PTEN 3'-UTR luciferase activity. AtT-20 cells were transfected with miR-106b mimics, miR-106b inhibitor, PTEN expression plasmid, and miR-106b mimics + PTEN expression plasmid respectively, and the changes in cellular proliferation and invasion were observed via MTT method and transwell assay respectively. PTEN messenger RNA (mRNA) expression was determined by quantitative real-time PCR, and western blotting was performed to detect the expression of PTEN, PI3K, AKT, and pAKT. miR-106b showed up-regulation in invasive pituitary tumor tissue: the expression level was significantly up-regulated compared with normal tissues and the non-invasive pituitary tumor tissue (P < 0.05). The positive rate of PTEN protein expression in invasive pituitary tumor tissues was significantly lower than in normal and non-invasive tissues (P < 0.01). Dual-luciferase reporter gene assay showed that miR-106b could bind to the 3'-UTR of PTEN specifically and significantly inhibited the luciferase activity, cutting the 46 % (P < 0.01). Down-regulation of miR-106b or up-regulation of PTEN could suppress cell proliferation and invasion of AtT-20 cells, and PTEN expression plasmid could partially simulate the function of miR-106b. Expression of PTEN mRNA and protein decreased significantly in AtT-20 cells overexpressing miR-106b. The expression levels of PI3K and p-AKT were significantly inhibited by miR-106b inhibitor and increased by miR-106b mimics. The expression of miR-106b showed up-regulation in pituitary tumor tissues, while the protein expression of PTEN presented opposite results. The findings of this study further demonstrated that miR-106b as an oncogene regulated the pituitary tumor cell proliferation and invasion in vitro by directly targeting PTEN through the PI3K/AKT signaling pathway. Our study suggests that miR-106b and PTEN are likely to serve as potential diagnostic biomarkers or therapeutic targets for pituitary tumor treatment in the future.
Lu B, Sheng Y, Zhang J, et al.The altered microRNA profile in andrographolide-induced inhibition of hepatoma tumor growth.
Gene. 2016; 588(2):124-33 [PubMed
] Related Publications
BACKGROUND: MicroRNAs (miRNAs) have been reported to play critical roles in regulating gene expression in tumor development. Natural compound andrographolide (Andro), isolated from medicinal herb Andrographis paniculata, was reported to inhibit hepatoma tumor growth in our previous studies. The present study aims to observe the altered miRNAs profile and related signaling pathways involved in Andro-induced inhibition on hepatoma tumor growth.
RESULTS: The inhibition on hepatoma tumor growth induced by Andro (10mg/kg) was found in a xenograft mouse tumor model in vivo. The results of miRNAs chip analysis showed that the expression of 22 miRNAs was increased, whereas the expression of other 10 miRNAs was decreased after Andro treatment. Further, the increased expression of miR-222-3p, miR-106b-5p, miR-30b-5p, and miR-23a-5p was confirmed in hepatoma Hep3B and SMCC7721 cells in vitro after cells were treated with Andro (50μM) for the indicated time. Functional annotation of the target genes based on the differentially expressed miRNAs demonstrated that the majority of the genes were involved in a variety of signaling pathways, including miRNAs in cancer, mitogen-activated protein kinases (MPAKs), focal adhesion. Furthermore, the expression of 24 target genes (total 31) involved in above signaling pathways based on miRNAs analysis was found to be consistent with the alteration of miRNAs.
CONCLUSIONS: The results demonstrate that Andro alters the expression of miRNAs profile and downstream signals, which may contribute to its inhibition on hepatoma tumor growth.
BACKGROUND: MicroRNA-106b (miR-106b) was recently identified as an oncogene participating in cancer progression. Transforming growth factor β1(TGF-β1) is an indispensable cytokine regulating the local microenvironment, thereby promoting cervical cancer progression. However, the roles of miR-106b in cervical carcinoma progression and TGF-β1-involvement in the tumorigenesis of cervical cancer remain unknown.
METHODS: The expression of miR-106b in human cervical specimens was detected by real-time PCR analysis and in situ hybridization assay. The effect of miR-106b on cell migration was analyzed by scratch and transwell assays. TGF-β1 was used to induce cell migration. The expression of the miR-106b target gene DAB2 in human cervical tissues and cell lines were measured by qRT-PCR, western blot and immunohistochemistry. Dual-luciferase reporter assay was used to identify DAB2 as a miR-106b-directed target gene.
RESULTS: miR-106b was frequently up-regulated in human cervical carcinoma specimens and cervical cancer cell lines. Over-expression of miR-106b significantly promoted HeLa and SiHa cells migration. Likewise, inhibition of miR-106b decreased HeLa and SiHa cells migration. The multifunctional cytokine TGF-β facilitates metastasis in cervical carcinoma. miR-106b inhibitor treatment decreased the TGF-β1-stimulated migration of HeLa and SiHa cells. DAB2, a predicted target gene of miR-106b, was inhibited by TGF-β1 partly through miR-106b and was involved in TGF-β1-induced cervical cancer cell migration. The expression of DAB2 was low in cervical cancer tissues, and negatively correlated with miR-106b expression. Finally, DAB2 was identified as a miR-106b-directed target gene by dual-luciferase reporter assay.
CONCLUSION: Our data suggest that the TGF-β1/miR-106b/DAB2 axis may be involved in the pathogenesis of cervical carcinoma.
Alarmo EL, Havunen R, Häyrynen S, et al.Bone morphogenetic protein 4 regulates microRNA expression in breast cancer cell lines in diverse fashion.
Genes Chromosomes Cancer. 2016; 55(3):227-36 [PubMed
] Related Publications
Bone morphogenetic protein 4 (BMP4) is a remarkably powerful inhibitor of breast cancer cell proliferation, but it is also able to induce breast cancer cell migration in certain cellular contexts. Previous data demonstrate that BMP4 controls the transcription of a variety of protein-coding genes, but not much is known about microRNAs (miRNA) regulated by BMP4. To address this question, miRNA expression profiles following BMP4 treatment were determined in one mammary epithelial and seven breast cancer cell lines using microarrays. While the analysis revealed an extensive variation in differentially expressed miRNA across cell lines, four miRNAs (miR-16-5p, miR-106b-5p, miR-23a-3p, and miR-23b-3p) were commonly induced in a subset of breast cancer cells upon BMP4 treatment. Inhibition of their expression demonstrated an increase in BT-474 cell number, indicating that they possess tumor suppressive properties. However, with the exception of miR-106b-5p, these effects were independent of BMP4 treatment. Scratch assay with miR-16-5p and miR-106b-5p inhibitors on BMP4-treated MDA-MB-231 cells resulted in enhanced cell migration, suggesting that these miRNAs are engaged in BMP4-induced motility. Taken together, we have for the first time characterized the BMP4-induced miRNA expression profiles in breast cancer cell lines, showing that induced miRNAs contribute to the fine-tuning of proliferation and migration phenotypes.
Lin N, Zhou Y, Lian X, Tu YExpression of microRNA-106b and its clinical significance in cutaneous melanoma.
Genet Mol Res. 2015; 14(4):16379-85 [PubMed
] Related Publications
MicroRNA-106b (miR-106b) is overexpressed in various types of cancers and is associated with the regulation of carcinogenic processes. However, its clinical significance in cutaneous melanoma has not been reported. qRT-PCR was performed to examine the expression of miR-106b in 15 cases of dysplastic nevi, 17 cases of melanoma metastases, and 97 cases of primary cutaneous melanoma tissue samples. Survival rate was determined with Kaplan-Meier and statistically analyzed with the log-rank method between groups. Survival data were evaluated through multivariate Cox regression analysis. Significant differences in miR-106b expression were shown between dysplastic nevi and primary cutaneous melanomas (P < 0.01), between primary melanomas and metastatic cutaneous melanomas (P < 0.01), and between primary cutaneous melanomas and metastatic cutaneous melanomas (P < 0.001). We found that high miR-106b expression was correlated with Breslow thickness (P = 0.002), tumor ulceration (P = 0.002), and advanced clinical stage (P < 0.001). The patients with high miR-106b expression showed shorter 5-year overall survival than those with low miR-106b expression (P = 0.02; log-rank test). Multivariate regression analysis showed that the status of miR-106b expression was an independent prognostic factor for overall survival (HR = 2.09, 95%CI: 1.11-10.26, P = 0.02). This study showed that miR-106b may contribute to the progression of cutaneous melanoma and its up-regulation may be independently associated with poor prognosis of cutaneous melanoma. This suggests that miR-106b might serve as a promising biological marker for further risk stratification in the management of cutaneous melanoma.
Li Y, Chen D, Su Z, et al.MicroRNA-106b functions as an oncogene in renal cell carcinoma by affecting cell proliferation, migration and apoptosis.
Mol Med Rep. 2016; 13(2):1420-6 [PubMed
] Related Publications
Kidney cancer is the 14th most common cancer in the world and its prognosis remains poor due to difficult early detection and treatment. Therefore, the identification of biomarkers for early-stage renal cell carcinoma (RCC) is important. MicroRNA-106b (miR-106b) has been described as an oncogene in several types of human cancer. Previous microarray studies have suggested that miR-106b was significantly upregulated in RCC tissues compared with paired normal kidney tissues and may be a promising biomarker for the prediction of early metastasis following nephrectomy. The present study aimed to determine the expression and function of miR-106b in RCC. The expression of miR-106b in RCC tissues and cells, and in paired normal tissues and cells was determined by reverse transcription quantitative polymerase chain reaction, based on the previous sequencing results of miRNAs. Furthermore, a wound scratch assay, MTT assay and flow cytometry were performed to examine the functions of miR-106b on cell migration, proliferation and apoptosis. The results demonstrated that miR-106b was upregulated in RCC tissues and cell lines compared with control normal tissues and cell lines. Downregulation of miR-106b with a synthesized inhibitor suppressed cell migration and proliferation and induced renal cancer cell apoptosis, suggesting that miR-106b can be characterized as an oncogene in RCC. To the best of our knowledge, the present study was the first to reveal that miR-106b is upregulated and affects cellular migration, proliferation and apoptosis in RCC. Further studies are required to examine the role and target genes of miR-106b in RCC.
Pancreatic cancer is one of the major malignancies and cause for mortality across the world, with recurrence and metastatic progression remaining the single largest cause of pancreatic cancer mortality. Hence it is imperative to develop novel biomarkers of pancreatic cancer prognosis. The E3 ubiquitin ligase ITCH has been previously reported to inhibit the tumor suppressive Hippo signaling by suppressing LATS1/2 in breast cancer and chronic lymphocytic leukemia. However, the role of ITCH in pancreatic cancer progression has not been described. Here we report that ITCH transcript and protein expression mimic metastatic trait in pancreatic cancer patients and cell lines. Loss-of-function studies of ITCH showed that the gene product is responsible for inducing metastasis in vivo. We furthermore show that hsa-miR-106b, which itself is down regulated in metastatic pancreatic cancer, directly interacts and inhibit ITCH expression. ITCH and hsa-miR-106b are thus potential biomarkers for pancreatic cancer prognosis.
Zheng L, Zhang Y, Lin S, et al.Down-regualtion of miR-106b induces epithelial-mesenchymal transition but suppresses metastatic colonization by targeting Prrx1 in colorectal cancer.
Int J Clin Exp Pathol. 2015; 8(9):10534-44 [PubMed
] Free Access to Full Article Related Publications
Accumulating evidence identified that epithelial-mesenchymal transition (EMT) is acquired during progression to metastatic, but whether it is an absolute requirement is still controversial. MiR-106b has been confirmed to promote cancer cell proliferation; however few studies are available on its functions in EMT and metastasis in colorectal cancer (CRC). In this study, we found that knocking down miR-106b induced EMT conferring migratory and invasive properties. MiR-106b knockdown induced cytoskeletal reorganization through staining intracellular F-actin. The expression of Rho GTPases (Rac1 and Cdc42) and Tiam1 was significantly enforced after miR-106b down-regulation. However, miR-106b knocking down could suppress metastatic colonization in vivo. Correspondingly, over expression of miR-106b obtained an opposite effect. We identified Prrx1 was a direct target of miR-106b through using target prediction algorithms and dual-Luciferase reporter assay. Moreover, Moreover, we also found TGF-β1 could down-regulate miR-106b, and simultaneously miR-106b also influences the expression of TGF-β1, establishing a negative feedback loop to regulate the expression of Prrx1 together. Taken together, these findings demonstrated that miR-106b knockdown could induce EMT which conferring cells migratory and invasive properties but could not accomplish distant metastatic colonization efficiently.
This is a systematic review of studies investigating the prognostic value of different microRNAs (miRs) in renal cell carcinoma (RCC). Twenty-seven relevant studies were identified, with a total of 2578 subjects. We found that elevated expression of miR-21, miR-1260b, miR-210, miR-100, miR-125b, miR-221, miR-630, and miR-497 was associated with a poor prognosis in RCC patients. Conversely, decreased expression of miR-106b, miR-99a, miR-1826, miR-215, miR-217, miR-187, miR-129-3p, miR-23b, miR-27b, and miR-126 was associated with a worse prognosis. We performed meta-analyses on studies to address the prognostic value of miR-21, miR-126, miR-210, and miR-221. This revealed that elevated miR-21 expression was associated with shorter overall survival (OS; hazard ratio [HR], 2.29; 95% confidence interval [CI], 1.28-4.08), cancer specific survival (CSS; HR, 4.16; 95% CI, 2.49-6.95), and disease free survival (DFS; HR, 2.15; 95% CI, 1.16-3.98). The decreased expression of miR-126 was associated with shorter CSS (HR, 0.35; 95% CI, 0.15-0.85), OS (HR, 0.45; 95% CI, 0.30-0.69), and DFS (HR 0.30; 95% CI, 0.18-0.50). Our comprehensive systematic review reveals that miRs, especially miR-21 and miR-126, could be promising prognostic markers and useful therapeutic targets in RCC.
Recent studies have shown that circulating microRNAs are a potential biomarker in various types of malignancies. The aim of this study was to investigate the feasibility of using serum exosomal microRNAs as novel serological biomarkers for hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). We measured the serum exosomal microRNAs and serum circulating microRNAs in patients with CHB (n=20), liver cirrhosis (LC) (n=20) and HCC (n=20). Serum exosomal microRNA was extracted from 500 μl of serum using an Exosome RNA Isolation kit. The expression levels of microRNAs were quantified by real-time PCR. The expression levels of selected microRNAs were normalized to Caenorhabditis elegans microRNA (Cel-miR-39). The serum levels of exosomal miR-18a, miR-221, miR-222 and miR-224 were significantly higher in patients with HCC than those with CHB or LC (P<0.05). Further, the serum levels of exosomal miR-101, miR-106b, miR-122 and miR-195 were lower in patients with HCC than in patients with CHB (P=0.014, P<0.001, P<0.001 and P<0.001, respectively). There was no significant difference in the levels of miR-21 and miR-93 among the three groups. Additionally, the serum levels of circulating microRNAs showed a smaller difference between HCC and either CHB or LC. This study suggests that serum exosomal microRNAs may be used as novel serological biomarkers for HCC.
In recent years, not only has the role of miRNAs in cancer become increasingly clear but also their utilization as potential biomarkers and therapeutic targets has gained ground. Although the importance of dietary stilbenes such as resveratrol and pterostilbene as anti-cancer agents is well recognized, our understanding of their miRNA-targeting capabilities is still limited. In our previous study, we reported that resveratrol downregulates PTEN-targeting members of the oncogenic miR-17 family, which are overexpressed in prostate cancer. This study investigates the resveratrol and pterostilbene induced miRNA-mediated regulation of PTEN in prostate cancer. Here, we show that both compounds decrease the levels of endogenous as well as exogenously expressed miR-17, miR-20a and miR-106b thereby upregulating their target PTEN. Using functional luciferase reporter assays, we demonstrate that ectopically expressed miR-17, miR-20a and miR-106b directly target PTEN 3'UTR to reduce its expression, an effect rescued upon treatment with resveratrol and pterostilbene. Moreover, while stable lentiviral expression of miR-17/106a significantly decreased PTEN mRNA and protein levels and conferred survival advantage to the cells, resveratrol and more so pterostilbene was able to dramatically suppress these effects. Further, pterostilbene through downregulation of miR-17-5p and miR-106a-5p expression both in tumors and systemic circulation, rescued PTEN mRNA and protein levels leading to reduced tumor growth in vivo. Our findings implicate dietary stilbenes as an attractive miRNA-mediated chemopreventive and therapeutic strategy, and circulating miRNAs as potential chemopreventive and predictive biomarkers for clinical development in prostate cancer.
We previously showed that C1orf24 expression is increased in thyroid carcinomas. Nonetheless, the mechanism underlying C1orf24 deregulation is not fully understood. It has been widely demonstrated that microRNAs are involved in post-transcriptional gene regulation in several diseases, including cancer. Using in silico prediction approach, five microRNAs that bind to the 3'-untranslated region (3'-UTR) of C1orf24 were identified. The expression of two selected microRNAs (miR-17-5p, miR-106b) and the expression of C1orf24 were tested in 48 benign and malignant thyroid lesions and in five thyroid carcinoma cell lines. miR-106b was down-regulated in thyroid cancer specimens and thyroid carcinoma cell lines, while C1orf24 expression was markedly increased. To demonstrate that miR-106b reduces C1orf24 expression, follicular (WRO) and papillary (TPC1) thyroid carcinoma cell lines were transiently transfected with miR-106b mimic. Ectopic expression of the miR-106b mimic significantly inhibits C1orf24 mRNA and protein expression in both WRO and TPC1 cells. Dual-luciferase report assays demonstrated that miR-106b directly targets C1orf24 by binding its 3'-UTR. Moreover, miR-106b-mediated down-regulation of C1orf24 expression increased apoptosis and inhibited migration. We additionally demonstrated that siRNA against C1orf24 significantly decreased its expression, inhibited cell migration and cell cycle progression while induced apoptosis. In summary, our findings not only provide new insights into molecular mechanism associated with C1orf24 overexpression in thyroid carcinomas but also show that C1orf24 might increase proliferation and cell migration. Thus, decreasing C1orf24 levels, by restoring miR-106b function, may have therapeutic implications.
BACKGROUND: Radioresistance is a challenge in the treatment of patients with colorectal cancer (CRC). Individuals display different therapeutic responses to preoperative radiotherapy, and the need of targeted therapies is urgent. MicroRNAs (miRNAs) are involved in essential biological activities, including chemoresistance and radioresistance. Several research studies have indicated that miRNA played an important role in sensitizing cells to ionizing radiation (IR). MiR-106b, a member of the miR-106b-25 cluster, is frequently dysregulated in many human cancers, including CRC. However, the function of miR-106b in radioresistance is currently poorly understood.
METHODS: A series of in vitro and in vivo studies were performed to investigate the roles of miR-106b on cell radioresistance in CRC.
RESULTS: We found overexpression of miR-106b could induce resistance to IR in vitro and in vivo in SW620 cells. Correspondingly, knocking down miR-106b in SW480 yielded the opposite effect. In addition, overexpression of miR-106b could enhance the tumour-initiating cell capacity without or with IR condition, such as the colony sphere formation capacity and the upregulation of stemness-related genes (CD133, Sox2). We further identified PTEN and p21 as novel direct targets of miR-106b by using target prediction algorithms and a luciferase assay. Overexpression of miR-106b reduced the expression of PTEN and p21 and increased the expression of p-AKT, which is a downstream of PTEN. Restoring the expression of PTEN or p21 in stably miR-106b-overexpressed cells could rescue the effect of miR-106b on cell radioresistance. Together, the acquisition of tumour-initiating cell capacity endowed CRC cells with the potential of resistance to irradiation.
CONCLUSIONS: These observations illustrated that miR-106b could induce cell radioresistance by directly targeting PTEN and p21, this process was accompanied by tumour-initiating cell capacity enhancement, which is universally confirmed to be associated with radioresistance. Our data suggested that miR-106b at least partly induces cell radioresistance in CRC.
BACKGROUND: Growing evidence suggests that microRNAs (miRNAs) play an important role in tumor development, progression and metastasis. Aberrant miR-106b expression has been reported in several cancers. However, the role and underlying mechanism of miR-106 in colorectal cancer (CRC) have not been addressed.
METHODS: Quantitative RT-PCR(qRT-PCR) was performed to evaluate miR-106b levels in CRC cell lines and patient specimens. Cell proliferation was detected using MTT assay, and cell migration and invasion ability were evaluated by wound healing assay and transwell assay. The target gene of miR-106b was determined by qRT-PCR, western blot and luciferase assays.
RESULTS: miR-106b was significantly up-regulated in metastatic CRC tissues and cell lines, and high miR-106b expression was associated with lymph node metastasis and advanced clinical stage. In addition, miR-106b overexpression enhances, whereas miR-106b depletion reduces CRC cell migration and invasion. Moreover, we identify DLC1 as a direct target of miR-106b, reveal its expression to be inversely correlated with miR-106b in CRC samples and show that its re-introduction reverses miR-106b-induced CRC cell migration and invasion. Furthermore, survival analyses showed the patients with high mi-106b/low DLC1 had shorter overall survival (OS) and disease-free survival (DFS) rates, and confirmed miR-106b may be an independent prognostic factor for OS and DFS in CRC patients.
CONCLUSIONS: Our findings indicate that miR-106b promotes CRC cell migration and invasion by targeting DLC1. This miRNA may serve as a potential prognostic biomarker and therapeutic target for CRC.
Capicua (CIC) has been implicated in pathogenesis of spinocerebellar ataxia type-1 (SCA1) neurodegenerative disease and some types of cancer; however, the role of CIC in prostate cancer remains unknown. Here we show that CIC suppresses prostate cancer progression. CIC expression was markedly decreased in human prostatic carcinoma. CIC overexpression suppressed prostate cancer cell proliferation, invasion, and migration, whereas CIC RNAi exerted opposite effects. We found that knock-down of CIC derepresses expression of ETV5 and CRABP1 in LNCaP and PC-3 cells, respectively, thereby promoting cell proliferation and invasion. We also discovered that miR-93, miR-106b, and miR-375, which are known to be frequently overexpressed in prostate cancer patients, cooperatively down-regulate CIC levels to promote cancer progression. Altogether, we suggest miR-93/miR-106b/miR-375-CIC-CRABP1 as a novel key regulatory axis in prostate cancer progression.
Jha P, Agrawal R, Pathak P, et al.Genome-wide small noncoding RNA profiling of pediatric high-grade gliomas reveals deregulation of several miRNAs, identifies downregulation of snoRNA cluster HBII-52 and delineates H3F3A and TP53 mutant-specific miRNAs and snoRNAs.
Int J Cancer. 2015; 137(10):2343-53 [PubMed
] Related Publications
Pediatric high-grade gliomas (HGGs) are highly malignant tumors that remain incurable and relatively understudied. The crucial role of noncoding RNAs (ncRNAs) has been reported in various cancers. However, the study on miRNAs in pediatric HGGs is scant and there is no report till date on the status of other small ncRNAs. Genome-wide microarray analysis was performed to investigate small ncRNA expression in pediatric HGG (n = 14) and compared to adult glioblastoma (GBM) signature. The validation of miRNAs and small nucleolar RNAs (snoRNAs) was done by real-time polymerase chain reaction. TP53 and H3F3A mutation-specific miRNA and snoRNA profiles were generated and analyzed. Pediatric HGGs showed upregulation of miR-17/92 and its paralog clusters (miR106b/25 and miR-106a/363), whereas majority of downregulated miRNAs belonged to miR379/656 cluster (14q32). Unsupervised hierarchical clustering identified two distinct groups. Interestingly, Group 2 with downregulated 14q32 cluster showed better overall survival. The miRNAs unique to pediatric HGG as compared to adult GBM were predicted to affect PDGFR and SMAD2/3 pathways. Similarities were seen between pediatric HGG and TP53 mutant miRNA profiles as compared to wild types. Several of H3F3A mutation-regulated genes were found to be the targets of H3F3A mutant-specific miRNAs. Remarkably, a significant downregulation of HBII-52 snoRNA cluster was found in pediatric HGGs, and was specific to H3F3A nonmutants. This is the first genome-wide profiling study on miRNAs and snoRNAs in pediatric HGGs with respect to H3F3A and TP53 mutations. The comparison of miRNA profiles of pediatric HGGs and adult GBM reiterates the overlaps and differences as also seen with their gene expression and methylation signatures.
Jin N, Jin X, Gu X, et al.Screening biomarkers of bladder cancer using combined miRNA and mRNA microarray analysis.
Mol Med Rep. 2015; 12(2):3170-6 [PubMed
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Biomarkers, such as microRNAs (miRNAs) may be useful for the diagnosis of bladder cancer. In order to understand the molecular mechanisms underlying bladder cancer, differentially expressed miRNAs (DE-miRNAs) and their target genes in bladder cancer were analyzed. In the present study, miRNA and mRNA expression profiles (GSE40355) were obtained from the Gene Expression Omnibus. These consisted of healthy bladder samples (n=8) and urothelial carcinoma samples (low-grade, n=8 and high-grade, n=8). DE-miRNAs and differentially expressed genes (DEGs) were identified using the limma package and the Benjamin and Hochberg method from the multtest package in R. Target genes of DE-miRNAs were screened. Associations between DEGs were investigated using STRING, and an interaction network was constructed using Cytoscape. Functional and pathway enrichment analyses were performed for DEGs from the interaction network. 87 DE-miRNAs and 2058 DEGs were screened from low-grade bladder cancer samples, and 40 DE-miRNAs and 2477 DEGs were screened from high-grade bladder cancer samples. DE-target genes were significantly associated with the regulation of cell apoptosis. Bladder cancer, non-small cell lung cancer and pancreatic cancer biological pathways were found to be enriched. The results of the present study demonstrated that E2F transcription factor 1, which is targeted by miR-106b, and cyclin-dependent kinase inhibitor 2A (CDKN2A) and V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog-2, which are targeted by miR-125b, participate in the bladder cancer pathway. In conclusion, DE-miRNAs in bladder cancer tissue samples and DE-targeted genes, such as miR-106b and CDKN2A, which were identified in the present study, may provide the basis for targeted therapy for breast cancer and enhance understanding of its pathogenesis.
Epithelial ovarian cancer (EOC) is the most lethal of the gynecological malignancies. Exploring the molecular mechanisms and major factors of invasion and metastasis could have great significance for the treatment and prognosis of EOC. Studies have demonstrated that microRNA 106b (miR-106b) may be a promising therapeutic target for inhibiting breast cancer bone metastasis, but the role of miR-106b in EOC is largely unknown. In this work, miRNA-106b expression was quantified in various ovarian tissues and tumors. Ovarian carcinoma cell lines were transfected with miR-106b, after which, cell phenotype and expression of relevant molecules was assayed. Dual-luciferase reporter assays and xenograft mouse models were also used to investigate miR-106b and its target gene. MiR-106b mRNA expression was found to be significantly higher in normal ovarian tissues and benign tumors than in ovarian carcinomas and borderline tumors (p < 0.01), and was negatively associated with differentiation (Well vs. Por & Mod) and the International Federation of Gynecology and Obstetrics (FIGO) staging (stage I/II vs. stage III/IV) in ovarian carcinoma (p < 0.05). MiR-106b transfection reduced cell proliferation; promoted G1 or S arrest and apoptosis (p < 0.05); suppressed cell migration and invasion (p < 0.05); reduced Ras homolog gene family member C (RhoC), P70 ribosomal S6 kinase (P70S6K), Bcl-xL, Matrix metallopeptidase 2 (MMP2), MMP9 mRNA and protein expression; and induced p53 expression (p < 0.05). Dual-luciferase reporter assays indicated that miR-106b directly targets RhoC by binding its 3'UTR. MiR-106b transfection also suppressed tumor development and RhoC expression in vivo in xenograft mouse models. This is the first demonstration that miR-106b may inhibit tumorigenesis and progression of EOC by targeting RhoC. The involvement of miR-106b-mediated RhoC downregulation in EOC aggression may give extended insights into molecular mechanisms underlying cancer aggression. Approaches aimed at overexpressing miR-106b may serve as promising therapeutic strategies for treating EOC patients.
Wang D, Tan J, Xu Y, et al.Identification of MicroRNAs and target genes involvement in hepatocellular carcinoma with microarray data.
Hepatogastroenterology. 2015 Mar-Apr; 62(138):378-82 [PubMed
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The aim of the study is to identify the differentially expressed microRNAs (miRNAs) between hepatocellular carcinoma (HCC) samples and controls and provide new diagnostic potential miRNAs for HCC. The miRNAs expression profile data GSE20077 included 7 HCC samples, 1 HeLa sample and 3 controls. Differentially expressed miRNAs (DE-miRNAs) were identified by t-test and wilcox test. The miRNA with significantly differential expression was chosen for further analysis. Target genes for this miRNA were selected using TargetScan and miRbase database. STRING software was applied to construct the target genes interaction network and topology analysis was carried out to identify the hub gene in the network. And we identified the mechanism for affecting miRNA function. A total of 54 differentially expressed miRNAs were identified, in which there were 13 miRNAs published to be related to HCC. The differentially expressed hsa-miR-106b was chosen for further analysis and PTPRT (Receptor-type tyrosine-protein phosphatase T) was its potential target gene. The target genes interaction network was constructed among 33 genes, in which PTPRT was the hub gene. We got the conclusion that the differentially expressed hsa-miR-106b may play an important role in the development of HCC by regulating the expression of its potential target gene PT-PRT.
Wei Z, Zhou C, Liu M, et al.MicroRNA involvement in a metastatic non-functioning pituitary carcinoma.
Pituitary. 2015; 18(5):710-21 [PubMed
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PURPOSE: Pituitary carcinomas are extremely rare neoplasms, and molecular events leading to malignant pituitary transformation are largely unknown. Enhanced understanding of molecular mechanisms driving malignant pituitary progression would be beneficial for pituitary carcinoma diagnosis and treatment.
METHODS: Differential microRNA expression in paired primary and metastatic pituitary carcinoma specimens were detected using high-throughput human microRNA microarrays and TaqMan microRNA arrays. Three of significantly deregulated miRNAs were further confirmed using quantitative real-time PCR in the metastatic carcinoma, six atypical pituitary adenomas and eight typical pituitary adenomas. Target genes of microRNAs were bioinformatically predicated and verified in vitro by Western blotting and real-time PCR and in vivo by immunohistochemistry respectively.
RESULTS: We present a case of a 50-year-old woman harboring non-functioning pituitary carcinoma with multiple intracranial metastases, and identified up-regulation of miR-20a, miR-106b and miR-17-5p in the metastatic carcinoma as compared to the primary neoplasm. Furthermore, miR-20a and miR-17-5p were increased in the metastatic carcinoma and six atypical pituitary adenomas as compared to eight typical pituitary adenomas as measured by quantitative real-time PCR. Both PTEN and TIMP2 were bioinformatically predicated and confirmed in vitro as target genes of these three microRNAs. As semi-quantified by immunohistochemistry, PTEN was absent and TIMP2 was decreased in the metastatic pituitary carcinoma as compared to pituitary adenomas.
CONCLUSIONS: Our results suggest microRNA involvement in malignant pituitary progression, whereby increased miR-20a, miR-106b and miR-17-5p promote metastasis by attenuating PTEN and TIMP2 in pituitary carcinoma.
El-Halawany MS, Ismail HM, Zeeneldin AA, et al.Investigating the pretreatment miRNA expression patterns of advanced hepatocellular carcinoma patients in association with response to TACE treatment.
Biomed Res Int. 2015; 2015:649750 [PubMed
] Free Access to Full Article Related Publications
Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents-doxorubicin and cisplatin-is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer.
Yang J, Zeng YIdentification of miRNA-mRNA crosstalk in pancreatic cancer by integrating transcriptome analysis.
Eur Rev Med Pharmacol Sci. 2015; 19(5):825-34 [PubMed
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OBJECTIVE: Pancreatic cancer is one of the most lethal diseases, and the pathogenesis remains largely unknown. To this end, we performed an integrated analysis of miRNA and mRNA expression data to explore the deregulation of miRNA and mRNA and regulatory processes underlying pancreatic cancer.
MATERIALS AND METHODS: We combined mRNA and miRNA expression data with miRNA target predictions to infer new miRNA regulation activities in pancreatic cancer. We first integrated miRNA and mRNA expression profiling separately to identify differently expressed miRNA and mRNA in pancreatic cancer. Then we adopted miRWalk databases prediction to obtain potential target genes of differently expressed miRNA, and compared these target genes to the gene list of integrated mRNA expression profiling to select differentially expressed miRNA-target gene whose expression was reversely correlated with that of corresponding miRNAs. Gene Ontology (GO) classification analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were employed to understand the functions and pathways of miRNA target genes. Finally we construct a miRNA-target gene regulatory network.
RESULTS: 42 differentially expressed miRNAs, 1376 differentially expressed mRNAs were identified by combining three expression profiles of miRNA and mRNA separately in pancreatic cancer, 146 miRNA target genes were found in the gene list of integrated mRNA expression profiling based on bioinformatics prediction. Functional annotation was performed to understand the functions and pathways of miRNA target genes. Finally, we constructed a miRNA-target gene regulatory network including 206 miRNA-target gene pairs. Five miRNAs (hsa-miR-130b, hsa-miR-106b, hsa-miR-181c, hsa-miR-153 and hsa-miR-125a-5p) demonstrated the highest connectivities, whereas three miRNAs (MYC, E2F1 and IL6) were the mRNAs with the highest connectivities.
CONCLUSIONS: Our findings may provide new insights into the knowledge of molecular mechanisms of pancreatic cancer and development of novel targeting therapies.
Inactivation of human SET domain containing protein 2 (SETD2) is a common event in clear cell renal cell carcinoma (ccRCC). However, the mechanism underlying loss of SETD2 function, particularly the post-transcriptional regulatory mechanism, still remains unclear. In the present study, we found that SETD2 was downregulated and inversely correlated with high expression of miR-106b-5p in ccRCC tissues and cell lines. Over-expression of miR-106b-5p resulted in the decreased mRNA and protein levels of SETD2 in ccRCC cells. In an SETD2 3'-UTR luciferase reporter system, miR-106b-5p downregulated the luciferase activity, and the effects were abolished by mutating the predicted miR-106b-5p binding site. Moreover, attenuation of miR-106b-5p induced cell cycle arrest at G0/G1 phase, suppressed cell proliferation, enhanced processing of caspase-3, and promoted cell apoptosis in ccRCC cells, whereas these effects were reversed upon knockdown of SETD2. In addition, transfection of miR-106b-5p antagomir resulted in the increased binding of H3K36me3 to the promoter of p53 and enhanced its activity, as well as upregulated the mRNA and protein levels of p53, and the effects were also abolished by cotransfection with si-SETD2. Collectively, our findings extend the knowledge about the regulation of SETD2 at the posttranscriptional level by miRNA and regulatory mechanism downstream of SETD2 in ccRCC.
Battistella M, Romero M, Castro-Vega LJ, et al.The High Expression of the microRNA 17-92 Cluster and its Paralogs, and the Downregulation of the Target Gene PTEN, Is Associated with Primary Cutaneous B-Cell Lymphoma Progression.
J Invest Dermatol. 2015; 135(6):1659-67 [PubMed
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The oncogenic microRNA (miR) 17-92 cluster has a causative role in the lymphomagenesis of nodal B-cell lymphomas, by activating proliferation and inhibiting apoptosis. Here we analyzed primary cutaneous B-cell lymphomas for the miR-17-92 cluster and its paralogs miR-106a-363 and miR-106b-25. In 22 primary cutaneous diffuse large B-cell lymphomas, leg type (PCLBCL-LT) compared with 22 primary cutaneous follicle center lymphomas (PCFCLs), we found that miR-20a and miR-106a were overexpressed. Multivariate Cox analysis showed that higher miR-20a and miR-20b expression levels were associated with shorter disease-free and overall survival, independently from histological type. Gene expression profiling also showed a downregulation of 8 candidate target genes of miR-20a, miR-20b, and miR-106a in PCLBCL-LT compared with PCFCL. Among the candidate target genes, PTEN, NCOA3, and CAPRIN2 were confirmed to be underexpressed in PCLBCL-LT using quantitative reverse transcriptase-PCR on CD20-positive laser-microdissected tumor cells. In multivariate Cox analysis, lower PTEN mRNA expression level was associated with shorter disease-free survival (DFS), independently from the histological type. Altogether, this molecular and bioinformatic study of 44 patient skin biopsy samples showed that the oncogenic miR-17-92 cluster and its paralogs were involved in cutaneous B-cell lymphoma progression, and that the downregulation of the target gene PTEN was associated with shorter DFS.
ZBTB4 is a transcriptional repressor and examination of publically-available microarray data sets demonstrated an inverse relationship in the prognostic value and expression of ZBTB4 and the histone methyltransferase EZH2 in tumors from breast cancer patients. The possibility of functional interactions between EZH2 and ZBTB4 was investigated in breast cancer cells and the results showed that EZH2 is directly suppressed by ZBTB4 which in turn is regulated (suppressed) by miR-106b and other paralogues from the miR-17-92, miR-106b-25 and miR-106a-363 clusters that are highly expressed in breast and other tumors. ZBTB4 also acts a suppressor of specificity protein (Sp) transcription factors Sp1, Sp3 and Sp4, and RNA interference studies show that Sp proteins are required for EZH2 expression. The prediction analysis results from breast cancer patient array data sets confirm an association of Sp1-dependent EZH2 gene signature with decreased survival of breast cancer patients. Disruption of oncogenic miR-ZBTB4 signaling axis by anticancer agent such as betulinic acid that induce down-regulation of Sp proteins in breast cancer cells resulted in inhibition of tumor growth and colonization of breast cancer cells in a mouse model. Thus, EZH2 is reciprocally regulated by a novel signaling network consisting of Sp proteins, oncogenic miRs and ZBTB4, and modulation of this gene network is a novel therapeutic approach for treatment of breast cancer and possibly other cancers.
BACKGROUND: MicroRNA-106b (miR-106b) is a member of the miR-106b ~ 25 cluster. It has been reported that miR-106b acts as an oncogene and is upregulated in many human cancers. However, the prognostic value of miR-106b in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to investigate the clinical significance of miR-106b expression in HCC.
METHODS: We determined the expression level of miR-106b in 104 cases of paired HCC and adjacent non-tumor tissues by quantitative real-time PCR (qRT-PCR). The correlation between miR-106b expression and prognosis of HCC was studied by univariate and multivariate analysis. Multivariate analysis of the prognostic factors was performed with Cox proportional hazards model.
RESULTS: MiR-106b expression was significantly upregulated in as high as 76.0% of HCC tissues, compared with their non-tumor counterparts (P < 0.001). High miR-106b expression was significantly associated with large tumor size (P = 0.019) and vascular invasion (P = 0.016). Kaplan-Meier analysis showed that patients with high miR-106b expression had a worse overall survival than patients with low miR-106b expression (log-rank P = 0.004). The multivariate Cox regression analysis indicated that miR-106b expression was an independent prognostic factor for overall survival (HR, 2.002; 95% CI, 1.130-6.977; P = 0.027).
CONCLUSION: Our data indicated that miR-106b expression was significantly upregulated in HCC and could serve as a potential unfavorable prognostic biomarker.
VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_226.
He XX, Kuang SZ, Liao JZ, et al.The regulation of microRNA expression by DNA methylation in hepatocellular carcinoma.
Mol Biosyst. 2015; 11(2):532-9 [PubMed
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UNLABELLED: Emerging evidence indicates that microRNAs (miRNAs) are often dysregulated and play a fundamental role in hepatocellular carcinoma (HCC). However, the mechanism underlying miRNA dysregulation is still elusive. In the present study, we adopted an integrated analysis strategy combining data from genome-wide methylated DNA immunoprecipitation chip and miRNA expression microarray to study the regulation of DNA methylation on miRNA expression in HCC. We first characterized 864 differentially methylated regions (DMRs) located in 236 miRNA regions between cancerous and normal hepatocytes in HCC. We observed that the occurrence of miRNA DNA hypomethylation was more common than its hypermethylation while miRNA DNA hypermethylation was usually found in CpG islands. Then through correlation analysis between miRNA methylation and expression data, we identified 10 dysregulated miRNAs under the potential regulation of DNA methylation in HCC. Five of them (miR-148a, miR-375, miR-195, miR-497 and miR-378) were in hypermethylation and down-regulation status, while another five (miR-106b, miR-25, miR-93, miR-23a and miR-27a) were in hypomethylation and up-regulation status in HCC. Bioinformatics analysis showed that miR-148a may form a negative feedback loop with its targets DNMT1 and DNMT3B and the expression of the miR-195/497 cluster may be affected not only by their hypermethylated promoter region but also by their hypermethylated transcription factors NEUROG2 and DDIT3.
CONCLUSION: our preliminary data and bioinformatics analysis suggest that DNA methylation plays an important and complex role in the regulation of miRNA expression in HCC, which may provide insights into the pathogenesis of HCC and thus may be used for diagnosis and intervention.
Gong C, Qu S, Lv XB, et al.BRMS1L suppresses breast cancer metastasis by inducing epigenetic silence of FZD10.
Nat Commun. 2014; 5:5406 [PubMed
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BRMS1L (breast cancer metastasis suppressor 1 like, BRMS1-like) is a component of Sin3A-histone deacetylase (HDAC) co-repressor complex that suppresses target gene transcription. Here we show that reduced BRMS1L in breast cancer tissues is associated with metastasis and poor patient survival. Functionally, BRMS1L inhibits breast cancer cells migration and invasion by inhibiting epithelial-mesenchymal transition. These effects are mediated by epigenetic silencing of FZD10, a receptor for Wnt signalling, through HDAC1 recruitment and histone H3K9 deacetylation at the promoter. Consequently, BRMS1L-induced FZD10 silencing inhibits aberrant activation of WNT3-FZD10-β-catenin signalling. Furthermore, BRMS1L is a target of miR-106b and miR-106b upregulation leads to BRMS1L reduction in breast cancer cells. RNA interference-mediated silencing of BRMS1L expression promotes metastasis of breast cancer xenografts in immunocompromised mice, whereas ectopic BRMS1L expression inhibits metastasis. Therefore, BRMS1L provides an epigenetic regulation of Wnt signalling in breast cancer cells and acts as a breast cancer metastasis suppressor.