Research IndicatorsGraph generated 01 September 2019 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 01 September, 2019 using data from PubMed, MeSH and CancerIndex
Specific Cancers (10)
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)||MIR1301 Function in Cancer||Effect|
-liver cancer (1)
|inhibit cell migration (1)|
inhibit cell invasion (1)
promote apoptosis (1)
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-1301 associations with cancer and associated genes.
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: MIR1301 (cancer-related)
Wang X, Hu K, Chao Y, Wang LLncRNA SNHG16 promotes proliferation, migration and invasion of osteosarcoma cells by targeting miR-1301/BCL9 axis.
Biomed Pharmacother. 2019; 114:108798 [PubMed
] Related Publications
Long non-coding RNAs (lncRNAs) play a key role in regulating tumor growth and metastasis of osteosarcoma (OS). Recent studies have reported that lncRNA small nucleolar RNA host gene 16 (SNHG16) is highly expressed in OS tissues and contributes to the proliferation, migration and invasion of OS cells. However, the molecular mechanism involved in the oncogenic role of SNHG16 in OS remains poorly known. In the current study, we confirmed that SNHG16 expression was markedly up-regulated in OS tissues compared to paracancerous tissues. The elevated level of SNHG16 closely associated with advanced tumor stages, larger tumor size and more distance metastasis. Furthermore, OS patients with high SNHG16 level had a significant poorer overall survival compared to patients with low SNHG16 level. Knockdown of SNHG16 suppressed the proliferation, migration and invasion of U2OS and MG63 cells. Mechanistically, SNHG16 acted as a competing endogenous RNA (ceRNA) by directly interacting with miR-1301 and inversely regulated its abundance in OS cells. Notably, suppression of miR-1301 rescued SNHG16 knockdown attenuated OS cell proliferation, migration and invasion. SNHG16 knockdown reduced the expression of BCL9 protein in OS cells. Accordingly, BCL9 restoration facilitated the proliferation, migration and invasion of OS cells with SNHG16 knockdown. Collectively, these results suggest that SNHG16 is a potential prognostic biomarker for OS patients. SNHG16 promotes BCL9 expression by sponging miR-1301 to facilitate the proliferation, migration and invasion of OS cells.
Wen J, Wang H, Dong T, et al.STAT3-induced upregulation of lncRNA ABHD11-AS1 promotes tumour progression in papillary thyroid carcinoma by regulating miR-1301-3p/STAT3 axis and PI3K/AKT signalling pathway.
Cell Prolif. 2019; 52(2):e12569 [PubMed
] Related Publications
OBJECTIVES: Emerging evidences indicated the importance of long non-coding RNAs (lncRNAs) in the tumorigenesis and deterioration of malignant tumours. To our knowledge, the study about lncRNAs in papillary thyroid carcinoma (PTC) is still inadequate. ABHD11-AS1 was highly expressed in the PTC samples of The Cancer Genome Atlas database. This study focused on the biological function and mechanism of lncRNA ABHD11-AS1 in PTC.
MATERIALS AND METHODS: qRT-PCR analysis was used to examine the expression of ABHD11-AS1 in PTC tissues and cell lines. The prognostic significance of ABHD11-AS1 for the patients with PTC was analysed with Kaplan-Meier analysis. The effects of ABHD11-AS1 knockdown on the cell proliferation and metastasis were evaluated by in vitro functional assays and in vivo experiments. The molecular mechanism which contributed to the oncogenic role of ABHD11-AS1 in PTC was explored by conducting mechanism experiments. Rescue assays were carried out for final demonstration.
RESULTS: High expression of ABHD11-AS1 predicted poor prognosis for patients with PTC and promoted cell proliferation and metastasis in vitro and in vivo. ABHD11-AS1 was activated by the transcription factor STAT3. ABHD11-AS1 positively regulated PI3K/AKT signalling pathway. ABHD11-AS1 acted as a competitive endogenous (ce) RNA to upregulate STAT3 by sponging miR-1301-3p.
CONCLUSIONS: STAT3-induced lncRNA ABHD11-AS1 promoted PTC progression by regulating PI3K/AKT signalling pathway and miR-1301-3p/STAT3 axis.
Wang L, Hu K, Chao YMicroRNA-1301 inhibits migration and invasion of osteosarcoma cells by targeting BCL9.
Gene. 2018; 679:100-107 [PubMed
] Related Publications
Increasing reports demonstrated that miRNAs play a critical role in tumor development and progression. Previous studies revealed that miR-1301 was abnormally expressed in various cancers. However, its function and underlying mechanism in osteosarcoma (OS) remains unknown. In this study, miR-1301 expression was significantly down-regulated in both OS tissues and cell lines. Down-regulated miR-1301 was obviously associated with malignant clinical features and poor overall survival of OS patients. miR-1301 overexpression inhibited cell proliferation, migration and invasion. In addition, we identified BCL9 act as a direct target of miR-1301 by directly binding to its 3'-UTR. In clinical OS tissues, miR-1301 negatively correlated BCL9 expression. BCL9 was up-regulated in OS tissues and cells. BCL9 overexpression promoted OS progression. Moreover, restoration of BCL9 expression at least partially abolished the proliferation, migration and invasion of miR-1301 on OS cells. In conclusion, our data indicated that miR-1301 inhibited cell proliferation, migration and invasion of OS by targeting BCL9, and may represent a novel potential therapeutic target and prognostic marker for OS.
Zhang Z, Pan B, Lv S, et al.Integrating MicroRNA Expression Profiling Studies to Systematically Evaluate the Diagnostic Value of MicroRNAs in Pancreatic Cancer and Validate Their Prognostic Significance with the Cancer Genome Atlas Data.
Cell Physiol Biochem. 2018; 49(2):678-695 [PubMed
] Related Publications
BACKGROUND/AIMS: MicroRNAs (miRNAs) are promising biomarkers for pancreatic cancer (PaCa). However, systemic and unified evaluations of the diagnostic value of miRNAs are lacking. Therefore, we performed a systematic evaluation based on miRNA expression profiling studies.
METHODS: We obtained miRNA expression profiling studies from Gene Expression Omnibus (GEO) and ArrayExpress (AE) databases and calculated the pooled sensitivity, specificity, and summary area under a receiver operating characteristic (ROC) curve for every miRNA. According to the area under the curve (AUC), we identified the miRNAs with diagnostic potentiality and validated their prognostic role in The Cancer Genome Atlas (TCGA) data. Gene Ontology (GO) annotations and pathway enrichments of the target genes of the miRNAs were evaluated using bioinformatics tools.
RESULTS: Ten miRNA expression profiling studies including 958 patients were used in this diagnostic meta-analysis. A total of 693 miRNAs were measured in more than 9 studies. The top 50 miRNAs with high predictive values for PaCa were identified. Among them, miR-130b had the best predictive value for PaCa (pooled sensitivity: 0.73 [95% confidence intervals (CI) 0.44-0.91], specificity: 0.81 [95% CI 0.59-0.93], and AUC: 0.84 [95% CI 0.73-0.95]). We identified nine miRNAs (miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301) associated with overall survival in PaCa patients by combining our results with TCGA data. The results of a Cox model revealed that two miRNAs (miR-30a [hazard ratio (HR)=2.43, 95% CI 1.05-5.59; p=0.037] and miR-203 [HR=3.14, 95% CI 1.28-7.71; p=0.012]) were independent risk factors for prognosis in PaCa patients. In total, 405 target genes of the nine miRNAs were enriched with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and cancer-associated pathways such as Ras signaling pathways, phospholipase D signaling pathway, and AMP-activated protein kinase (AMPK) signaling pathway were revealed among the top 20 enriched pathways. There were significant negative correlations between miR-181b-1 and miR-125a expression levels and the methylation status of their promoter region.
CONCLUSION: Our study performed a systematic evaluation of the diagnostic value of miRNAs based on miRNA expression profiling studies. We identified that miR-23a, miR-30a, miR-125a, miR-129-1, miR-181b-1, miR-203, miR-221, miR-222, and miR-1301 had moderate diagnostic value for PaCa and predicted overall survival in PaCa patients.
Dou D, Yang S, Lin Y, Zhang JAn eight-miRNA signature expression-based risk scoring system for prediction of survival in pancreatic adenocarcinoma.
Cancer Biomark. 2018; 23(1):79-93 [PubMed
] Related Publications
PURPOSE: The purpose of this study was to establish a risk scoring system based on miRNAs to evaluate the prognosis in pancreatic adenocarcinoma.
METHODS: Using a miRNA microarray dataset (179 pancreatic adenocarcinoma specimens and 4 normal control specimens) from TCGA, differentially expressed miRNAs were identified. Cox proportional hazards regression analysis was used to identify significant prognostic miRNAs, with which a risk scoring system was established and tested on a validation set. Cox regression analysis was performed to identify independent predictors of survival from clinical characteristics. Stratified Cox regression analyses were conducted to unravel the associations of clinical characteristics with survival. Differentially expressed genes (DEGs) were screened followed by functional annotation of the DEGs.
RESULTS: Eight miRNAs (miR-1301, miR-598, miR-1180, miR-155, miR-496, miR-203, miR-193b, miR-135b) were independent predictors for survival. A risk scoring system was established with the 8 signature miRNAs. Upon Cox multivariate regression analysis, risk score, new tumor and targeted molecular therapy were independent predictors of prognosis. Stratified Cox regression analyses found that targeted molecular therapy and new tumor are associated with survival of patients. Survival-related DEGs were significantly enriched with regulation of transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway.
CONCLUSIONS: The study proposes 8-miRNA expression-based risk scoring system to predict prognosis in pancreatic adenocarcinoma. New tumor and targeted molecular therapy were independent predictors of prognosis. Transforming growth factor beta receptor, potassium ion transport and MAPK signaling pathway may be related to prognosis in pancreatic adenocarcinoma.
Peng X, Yan B, Shen YMiR-1301-3p inhibits human breast cancer cell proliferation by regulating cell cycle progression and apoptosis through directly targeting ICT1.
Breast Cancer. 2018; 25(6):742-752 [PubMed
] Related Publications
BACKGROUND: MiRNAs regulate a variety of biological processes, such as cell proliferation and apoptosis and play critical roles in cancer progression. Accumulating studies have demonstrated that miR-1301-3p could regulate the development and progression of multiple cancers, but its biological behaviors in breast cancer (BC) are still elusive.
METHODS: The expression of miR-1301-3p was determined in BC tissues and cell lines using quantitative real-time PCR analysis. The effects of miR-1301-3p on BC cell growth, proliferation, cell cycle distribution, and apoptosis were also explored in vitro using MTT, colony formation and Flow cytometry assays. The potential target gene of miR-1301-3p was determined by dual-luciferase reporter assay and verified by quantitative real-time PCR and western blot analysis.
RESULTS: We found the expression of miR-1301-3p was observably significantly down-regulated in BC tissues and cell lines. MiR-1301-3p expression in BC tissues was significantly associated with tumor size and clinical stage. Gain-of-function assays demonstrated that miR-1301-3p inhibited the cell growth and proliferation in breast cancer cell lines, MCF-7 and T-47D. Moreover, up-regulation of miR-1301-3p induced cell cycle G0/G1 phase arrest and apoptosis. Mechanistically, up-regulation of miR-1301-3p reduced the expression of CDK4, Cyclin D1, Bcl-2, but elevated the expression of p21, Bad and Bax. ICT1 was confirmed as a direct target of miR-1301-3p. Furthermore, ICT1 overexpression could partially reverse the effects of miR-1301-3p on BC cell proliferation, cell cycle progression and apoptosis.
CONCLUSION: Our observations suggested that miR-1301-3p inhibits cell proliferation via inducing cell cycle arrest and apoptosis through targeting ICT1, and might be a therapeutic target for BC.
Wu Q, Chen Z, Zhang G, et al.EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in triple negative breast cancer.
Acta Biochim Biophys Sin (Shanghai). 2018; 50(7):693-700 [PubMed
] Related Publications
Breast cancer is one of the most common malignancies in women. ERα, PR, and HER2 triple negative breast cancer (TNBC) is the current research focus because of the lack of effective targeted therapies. In our study, lentivirus systems were used to overexpress EZH2 and miR-1301 in TNBC cell lines. Western blot analysis and RT-qPCR were used to detect the protein and microRNA levels. The TCGA and Kaplan Meier plotter databases were used to analyze the EZH2 and miR-1301 expression levels in breast cancer. The effect of miR-1301 overexpression on cell proliferation, migration and colony formation were determined by using the sulforhodamine B (SRB) assay, wound healing assay and colony formation assay, respectively. Furthermore, an xenograft mouse model was used to investigate the function of miR-1301 overexpression in vivo. Finally, dual luciferase reporter assay was used to verify the binding site of EZH2 and miR-1301. We found that EZH2 induced the expression of miR-1301 in two TNBC cell lines, HCC1937 and HCC1806. Overexpression of miR-1301 suppressed TNBC cell proliferation, migration and colony formation, as well as the xenograft tumor growth in immunodeficient mice. Interestingly, miR-1301 inhibited the expression of EZH2 by binding to the 3'-UTR of EZH2 gene. These data suggest that EZH2 induces the expression of miR-1301 as a negative feedback control mechanism in TNBC.
Song XL, Huang B, Zhou BW, et al.miR-1301-3p promotes prostate cancer stem cell expansion by targeting SFRP1 and GSK3β.
Biomed Pharmacother. 2018; 99:369-374 [PubMed
] Related Publications
Cancer stem cells promote tumor progression, drug-resistance, and relapse, and many microRNAs (miRNAs) play critical roles in the expansion of cancer stem cells. In the present study, we investigated the role of miR-1301-3p in the expansion of prostate cancer stem cells; miR-1301-3p was significantly upregulated in prostate cancer cells and tissues compared with normal prostate cells and tissues. Sphere formation and side population assays suggested that miR-1301-3p promoted the expansion of prostate cancer stem cells, and increased the expression of prostate cancer stem cell-associated genes, such as OCT4, SOX2, NANOG, CD44, KLF4, c-MYC, and MMP2. MiR-1301-3p targeted Wnt pathway inhibitors, GSK3β and SFRP1, and inhibited their expression by directly binding to their 3' untranslated regions. TOP/FOP luciferase assays suggested that miR-1301-3p activated the Wnt pathway, which was confirmed by increased β-catenin expression in the nucleus. Furthermore, the miR-1301-3p level correlated negatively with GSK3β and SFRP1 in prostate cancer tissues. In summary, we found that miR-1301-3p promoted the expansion of prostate cancer stem cells by inhibiting GSK3β and SFRP1, and activating the Wnt pathway.
Liang L, Wei DM, Li JJ, et al.Prognostic microRNAs and their potential molecular mechanism in pancreatic cancer: A study based on The Cancer Genome Atlas and bioinformatics investigation.
Mol Med Rep. 2018; 17(1):939-951 [PubMed
] Free Access to Full Article Related Publications
Although certain biomarkers that are directly associated with the overall survival (OS) of patients with pancreatic adenocarcinoma (PAAD) have been identified, the efficacy of a single factor is limited to predicting the prognosis. The aim of the present study was to identify a combination micro (mi)RNA signature that enhanced the prognostic prediction for PAAD. Following analysis of the data available from The Cancer Genome Atlas (TCGA), 175 PAAD samples were selected for the present study, and the associations between 494 miRNAs and OS were investigated. The prognostic value of all miRNAs was analyzed by multivariate Cox regression, and the miRNAs were ranked according to the hazard ratio (HR) and P‑values. The top 5 miRNAs (miR‑1301, miR‑125a, miR‑376c, miR‑328 and miR‑376b) were significantly associated with OS (HR=0.139; 95% confidence interval, 0.043‑0.443; P<0.001), thus demonstrating that this panel was able to serve as an independent prognostic factor for PAAD. In addition, the present study also predicted the target genes of the top 10 miRNAs with the highest prognostic values using 12 different prediction software, and enrichment signaling pathway analyses elucidated that several pathways may be markedly associated with these miRNAs, including 'Pathways in cancer', 'Chronic myeloid leukemia', 'Glioma' and 'MicroRNAs in cancer'. Lastly, ubiquitin C, epidermal growth factor receptor, estrogen receptor 1, mitogen‑activated protein kinase 1, mothers against decapentaplegic homolog 4 and androgen receptor may be the hub genes revealed by STRING analysis. The present study identified several miRNAs, particularly a five‑miRNA‑pool, that may be reliable, independent factors for predicting survival in patients with PAAD. However, the underlying molecular mechanisms require further investigation in the future.
Bai QL, Hu CW, Wang XR, et al.Association between downexpression of miR-1301 and poor prognosis in patients with glioma.
Eur Rev Med Pharmacol Sci. 2017; 21(19):4298-4303 [PubMed
] Related Publications
OBJECTIVE: MiR-1301 has been shown to be frequently down-regulated in various tumors. However, the clinical significance of miR-1301 in human glioma is still unclear. The aim of this study was to evaluate the prognostic impact of the expressions of miR-1301 in patients with glioma.
PATIENTS AND METHODS: Quantitative Real-time PCR was used to determine the expression miR-1301 in glioma tissues and pair-matched adjacent normal tissues. The relationships between miR-1301 expression and clinicopathological parameters were examined by X2 test. Kaplan-Meier curves and multivariate Cox proportional models were used to study the impact on clinical outcome.
RESULTS: We observed that miR-1301 expression was significantly lower in glioma tissues compared with adjacent non-cancerous tissues (p<0.01). Also, low expressions of miR-1301 were significantly associated with high WHO grade (p<0.006), low Karnofsky performance score (KPS) (p=0.001), and large tumor size (p=0.004). Furthermore, the data of Kaplan-Meier survival analysis showed that low miR-1301 expression significantly associated with a worse overall survival (p=0.003) and disease-specific survival (p=0.001). Finally, the univariate and multivariate analysis showed that the miR-1301 expression was an independent predictor for both overall survival and disease-specific survival in glioma.
CONCLUSIONS: Our findings suggested lower miR-1301 expression resulted in poorer survival in patients with glioma, which may provide important indicators for further research.
Yang C, Xu Y, Cheng F, et al.miR-1301 inhibits hepatocellular carcinoma cell migration, invasion, and angiogenesis by decreasing Wnt/β-catenin signaling through targeting BCL9.
Cell Death Dis. 2017; 8(8):e2999 [PubMed
] Free Access to Full Article Related Publications
Metastasis is the major cause of the poor prognosis of hepatocellular carcinoma (HCC), and increasing evidence supports the contribution of miRNAs to cancer progression. However, the exact relationship between the level of miR-1301 expression and HCC cell migration, invasion, and angiogenesis remains largely unknown. Quantitative PCR was used to evaluate the level of miR-1301 expression in HCC tissues and cell lines. Transwell and tube-formation assays were used to measure the effects of miR-1301 on HCC cell migration and invasion, and angiogenesis, respectively. Luciferase reporter assays and western blotting were used to confirm the miR-1301 target genes. We found that miR-1301 was significantly downregulated in HCC tissues and cell lines. Low miR-1301 expression was associated with tumor vascular invasion and Edmondson grade. Gain- and loss-of-function assays demonstrated that miR-1301 inhibited the migration, invasion, epithelial-mesenchymal transition, and angiogenesis of HCC cells in vitro and in vivo. BCL9, upregulated in HCC tissues compared with matched adjacent normal tissues, was inversely correlated to miR-1301 levels in HCC tissues. Through reporter gene and western blot assays, BCL9 was shown to be a direct miR-1301 target. BCL9 overexpression could partially reverse the effects of miR-1301 on HCC cell migration and invasion. Most importantly, miR-1301 overexpression markedly suppressed the death of xenograft mouse models of cancer by reducing tumor load, metastasis, and host angiogenesis by downregulating BCL9, β-catenin, and vascular endothelial growth factor expression in tumor cells. Our observations suggested that miR-1301 inhibits HCC migration, invasion, and angiogenesis via decreasing Wnt/β-catenin signaling through targeting BCL9, and might be a therapeutic target for HCC.
OBJECTIVE: While tobacco smoking is a well-known risk factor for head and neck squamous cell carcinoma (HNSCC), the molecular mechanisms underlying tobacco-induced HNSCC remain unclear. This study sought to comprehensively identify microRNA (miRNA) alterations and evaluate their clinical relevance in smoking-induced HNSCC pathogenesis and progression.
MATERIALS AND METHODS: Using small RNA-sequencing data and clinical data from 145 HNSCC patients, we performed a series of differential expression and correlation analyses to identify a panel of tobacco-dysregulated miRNAs associated with key clinical characteristics in HNSCC. We then examined the expression patterns of these miRNAs in normal epithelial cell lines following exposure to cigarette smoke extract.
RESULTS: Our analyses revealed distinct panels of miRNAs to be dysregulated with smoking status and associated with additional clinical features, including tumor stage, metastasis, anatomic site, and patient survival. The differential expression of key miRNAs, including miR-101, miR-181b, miR-486, and miR-1301, was verified in cigarette-treated epithelial cell lines, suggesting their potential roles in the early development of smoking-related HNSCCs.
CONCLUSION: Specific alterations in miRNA expression may be traced to tobacco use and are associated with important HNSCC clinical characteristics. Future studies of these miRNAs may be valuable for furthering the understanding and targeted treatment of smoking-associated HNSCC.
Wang B, Wu H, Chai C, et al.MicroRNA-1301 suppresses tumor cell migration and invasion by targeting the p53/UBE4B pathway in multiple human cancer cells.
Cancer Lett. 2017; 401:20-32 [PubMed
] Related Publications
The p53 protein plays a critical role in preventing tumor development. Although numerous factors have been shown to directly or indirectly regulate p53, the mechanism of how microRNAs (miRNAs) modulate p53 remains unclear. Here, we identified miR-1301, a microRNA that regulates the activity and function of p53, by directly targeting the ubiquitination factor E4B (UBE4B), an E3 and E4 ubiquitin ligase. Notably, ectopic expression of miR-1301 inhibits dissemination and metastasis of tumor cells in a p53-dependent manner. Depletion of miR-1301 downregulates p53 function. Our results reveal that there is an inverse correlation between miR-1301 and UBE4B expression and p53 status in prostate cancer. Furthermore, low miR-1301 expression is often associated with incomplete methylation of its gene in human prostate tumors. Together, our results provide the first report indicating that miR-1301 functions as a tumor suppressor that inhibits tumor cell migration and invasion in multiple human cancer cells by regulating the UBE4B-p53 pathway.
Bi D, Ning H, Liu S, et al.miR-1301 promotes prostate cancer proliferation through directly targeting PPP2R2C.
Biomed Pharmacother. 2016; 81:25-30 [PubMed
] Related Publications
Prostate cancer is the leading cause of cancer deaths among men in the worldwide, it's important to find new prognostic factors and therapeutic targets. microRNAs play critical roles in the development and progression of prostate cancer. Here we revealed miR-1301 promoted prostate cancer progression. miR-1301 was upregulated in prostate cancer tissues and cells, overexpression of miR-1301 promoted anchorage-dependent and -independent growth using MTT analysis, colony formation analysis and soft agar growth analysis, whereas knockdown of miR-1301 suppressed anchorage-dependent and -independent growth. We also found overexpression of miR-1301 inhibited p27 expression and promoted Cyclin D1 expression, whereas knockdown of miR-1301 reduced this effect, suggesting miR-1301 promoted the G1/S transition. These results suggested miR-1301 promoted cell proliferation of prostate cancer. microRNAs can inhibit target mRNA translation or/and induce mRNA degradation, we found tumor suppresser PPP2R2C was the target of miR-1301, simultaneous downregualtion of PPP2R2C and miR-1301 promoted anchorage-dependent and -independent growth. These findings suggested miR-1301 promoted prostate cancer proliferation by inhibiting PPP2R2C, and might a therapeutic target for prostate cancer.
Chronic myeloid leukemia (CML) is a myeloproliferative disease. Imatinib (IM), the first line treatment for CML, is excessively expensive and induces various side effects in CML patients. Therefore, it is essential to investigate a new strategy for improving CML therapy. Our immunoblot data revealed that RanGTPase activating protein 1 (RanGAP1) protein levels increased by approximately 30-fold in K562 cells compared with those in normal cells. RanGAP1 is one of the important components of RanGTPase system, which regulates the export of nuclear protein. However, whether RanGAP1 level variation influences BCR-ABL nuclear export is still unknown. In this report, using shRNA to downregulate RanGAP1 expression level augmented K562 cell apoptosis by approximately 40% after treatment with 250 nM IM. Immunofluorescence assay also indicated that three-fold of nuclear BCR-ABL was detected. These data suggest that BCR-ABL nuclear entrapment induced by RanGAP1 downregulation can be used to improve IM efficacy. Moreover, our qRT-PCR data indicated a trend of inverse correlation between the RanGAP1 and microRNA (miR)-1301 levels in CML patients. MiR-1301, targeting the RanGAP1 3' untranslated region, decreased by approximately 100-fold in K562 cells compared with that in normal cells. RanGAP1 downregulation by miR-1301 transfection impairs BCR-ABL nuclear export to increase approximately 60% of cell death after treatment of 250 nM IM. This result was almost the same as treatment with 1000 nM IM alone. Furthermore, immunofluorescence assay demonstrated that Tyr-99 of nuclear P73 was phosphorylated accompanied with nuclear entrapment of BCR-ABL after transfection with RanGAP1 shRNA or miR-1301 in IM-treated K562 cells. Altogether, we demonstrated that RanGAP1 downregulation can mediate BCR-ABL nuclear entrapment to activate P73-dependent apoptosis pathway which is a novel strategy for improving current IM treatment for CML.
Li W, Han W, Ma Y, et al.P53-dependent miRNAs mediate nitric oxide-induced apoptosis in colonic carcinogenesis.
Free Radic Biol Med. 2015; 85:105-13 [PubMed
] Related Publications
Both miRNAs and nitric oxide (NO) play important roles in colonic inflammation and tumorigenesis. Resistance of colonic epithelial cells to apoptosis may contribute to tumor development. We hypothesized that some miRNAs could increase the resistance of colonic cancer cells to nitric oxide-induced apoptotic cell death. Here we show that NO induced apoptosis and stimulated expression of some miRNAs. Loss of p53 not only blocked NO-induced apoptosis but also dramatically inhibited the expression of NO-related miRNAs, such as miR-34, miR-203, and miR-1301. In addition, blockage of p53-dependent miRNAs significantly reduced NO-induced apoptosis. Furthermore, forced expression of these miRNAs rendered HT-29 cells, which are resistant to apoptosis with mutant p53, more sensitive to NO-induced apoptotic cell death. Most interestingly, in a colitis-associated colon cancer mouse model, the level of miRNAs dropped significantly, accompanied by downregulation of p21, which is a key target gene of p53. In human colorectal cancer samples, the expression of miR-34 significantly correlated with the level of inducible nitric oxide synthase (iNOS). We contend that increased NO production may select cells with low levels of p53-dependent miRNAs which contributes to human colonic carcinogenesis and tumor progression.
The Krüppel like factor 6 (KLF6) gene encodes multiple protein isoforms derived from alternative mRNA splicing, most of which are intimately involved in hepatocarcinogenesis and tumor progression. Recent bioinformatics analysis shows that alternative mRNA splicing of the KLF6 gene produces around 16 alternatively spliced variants with divergent or even opposing functions. Intriguingly, the full-length KLF6 (KLF6-FL) is a tumor suppressor gene frequently inactivated in liver cancer, whereas KLF6 splice variant 1 (KLF6-SV1) is an oncogenic isoform with antagonistic function against KLF6-FL. Compelling evidence indicates that miRNA, the small endogenous non-coding RNA (ncRNA), acts as a vital player in modulating a variety of cellular biological processes through targeting different mRNA regions of protein-coding genes. To identify the potential miRNAs specifically targeting KLF6-FL, we utilized bioinformatics analysis in combination with the luciferase reporter assays and screened out two miRNAs, namely miR-210 and miR-1301, specifically targeted the tumor suppressive KLF6-FL rather than the oncogenic KLF6-SV1. Our in vitro experiments demonstrated that stable expression of KLF6-FL inhibited cell proliferation, migration and angiogenesis while overexpression of miR-1301 promoted cell migration and angiogenesis. Further experiments demonstrated that miR-1301 was highly expressed in liver cancer cell lines as well as clinical specimens and we also identified the potential methylation and histone acetylation for miR-1301 gene. To sum up, our findings unveiled a novel molecular mechanism that specific miRNAs promoted tumorigenesis by targeting the tumor suppressive isoform KLF6-FL rather than its oncogenic isoform KLF6-SV1.
The relatively recent discovery of microRNAs has added a completely new dimension to the study of the regulation of tumor cells, but how they control cell behavior remains largely elusive. HepG2 cells were assigned to the miR-1301 group and the control group. RT-PCR, Western blotting, wound healing, the Transwell chamber migration and MTT assays, and apoptosis detection assays were used to analyze cell behavior of HepG2 cells after miR-1301 mimic transfection. Our study showed that miR-1301 was downregulated in HepG2 cells, and that miR-1301 inhibited migration and invasion of HepG2 cells and promoted cellular apoptosis after transfection with miR-1301 mimics. In addition, p53 mRNA and p53 protein expression was upregulated, and Bcl-2 and Bcl-xL mRNA and protein expression was downregulated in the miR-1301 group. These results indicate that miR-1301 may be an inhibitor of tumorigenesis in HepG2 cells.