High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin

Jingushi, Kentaro; Kashiwagi, Yuri; Ueda, Yuko; Kitae, Kaori; Hase, Hiroaki; Nakata, Wataru; Fujita, Kazutoshi; Uemura, Mamoru; Nonomura, Norio; Tsujikawa, Kazutake

doi:10.3892/ijo.2017.4016

Cited by 30 publications

(25 citation statements)

References 51 publications

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“…Fan, Y et al have indicated that miR-122 contributed to metastasis of ccRCC by regulating Dicer [27]. Furthermore, high level expression of miR-122 promoted malignant phenotypes in ccRCC [28]. The changing roles of miR-122 might result from sophisticated interactions in diverse tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway

Kong

Zhao

et al. 2019

Cell Cycle

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In the present study, we aimed to identify specific lncRNAs and miRNAs, as well as mRNAs, involved in bile duct carcinoma (BDC) and to further explore the way in which lncRNA UCA1 regulates cell metastasis ability. Differentially expressed RNAs were screened out from the TCGA database. In in vitro experiments, qRT-PCR was used to measure lncRNA UCA1, miR-122 and CLIC1 expression. We performed a dual luciferase assay to validate the target relationships among UCA1, CLIC1 and miR-122. The cell migration ability was measured by a wound healing assay, and Transwell assays were applied to detect cell invasive ability. Western blot analysis was employed to detect the expression of related proteins in the MAPK signaling pathway. According to the bioinformatics analysis, lncRNA UCA1 and CLIC1 were both significantly upregulated in BDC, while the expression of miR-122 declined compared with the normal group. The target relationship among UCA1, CLIC1 and miR-122 was verified. UCA1 promoted BDC cell migration and invasiveness, while miR-122 inhibited their progression. CLIC1 served as the downstream target gene of miR-122 and had opposite effects. The ERK/MAPK signaling pathway was activated after upregulating UCA1. LncRNA-UCA1 promoted the metastasis of BDC cells by regulating the expression of miR-122 and its downstream gene mRNA CLIC1 and promoted the activation of the ERK/MAPK pathway, which expanded the horizons of targeted therapy of cholangiocarcinoma.

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Section: Discussionmentioning

confidence: 99%

Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway

Kong

Zhao

et al. 2019

Cell Cycle

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“…ccRCC is highly invasive, nearly 60% patients present metastasis at the procedure of diagnosis and therapy [19] . Meanwhile, metastatic cancer is not sensitive to chemotherapy and radiotherapy [20] . So, 5-year survival rate of ccRCC becomes negative and is of great significance to the therapeutic effect of tumor.…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic predictor for clear cell renal cell carcinoma constructed by weighted gene co-expression correlation network analysis

Li¹,

Jin²,

Guo³

et al. 2020

Preprint

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Background Clear cell renal cell carcinoma (ccRCC) accounts the largest proportion of all types of renal tumor, it is highly invasive leading to shorter survival time of patients suffer from tumor. This study aims at constructing a new prognostic signature to provide a new reference for clinic work to adjust treatment protocols. Material and Methods Comprehensive gene expression profiles of ccRCC were downloaded from The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA), a genome-wide profiling analysis, was applied to investigate key genes associated with clinical traits. Cox regression analysis was conducted to screen prognostic gene in ccRCC. LASSO analysis was used to enhance the robust of correlated genes. Then, a prognostic signature was developed as an independent factor to predict outcomes of ccRCC patients. Results The co-expression network was constructed by WGCNA, 26 modules were identified in total, including a module (grey) showed no significance. By associating the features with clinic features, we selected three modules (pink, purple and turquoise) significantly associated with the overall survival(OS) of ccRCC patients. Univariate Cox analysis for genes from each module separately and then we used LASSO regression to screen the significant genes for selecting potential prognosis element-genes. 8 genes (CAPRIN2, IFI44, LTV1, ZNF320, MTHFR, XPOT, BCL3 and PAX2) finally reserved by multivariate COX regression. ScoreW was defined as a prognosis modelestablished by the final potential prognosis 8 genes. Multivariate regression suggested the ScoreW was an independent prognosis predicting element. ROC curve method was performed and the AUC value of ScoreW showed satisfied and attractive clinical prognosis importance. Conclusion Our findings provided the framework of co-expression gene modules of ccRCC and identified valuable prognostic method might be detection for ccRCC patients.

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“…Multiple miRNAs, including miR-138 [13], miR-122 [32], miR-101 [33], miR-206 [34], and miR-429 [35], have been dysregulated and play an important role in crucial cellular biological processes in ccRCC, including cell proliferation, migration, and invasion, as well as apoptosis. In the present study, we found that miR-146a was up-regulated in ccRCC tissues compared with the adjacent non-tumor tissue.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Regulated miR-146a Targets Cell Adhesion Molecule 2 to Promote Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma

Yang¹,

Zhao²,

Wang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: miR-146a has recently been shown to promote cell proliferation, migration, and invasion in many cancers, but the role of miR-146a in clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: Reverse transcription quantitative PCR (RT-qPCR) was performed to investigate the mRNA expression of miR-146a and CADM2 in ccRCC tissues. The luciferase reporter assay, Western blotting, and ChIP assay were carried out to explore the promoter and the transcription factor of miR-146a. Moreover, the effect of miR-146a and CADM2 on ccRCC cells was explored using methyl thiazolyl tetrazolium, colony formation, and migration and invasion assays. The luciferase reporter assay, RT-qPCR, western blotting, and immunofluorescence assay were carried out to investigate whether CADM2 is directly regulated by miR-146a. A tumor xenograft model and immunohistochemical staining were used to examine the carcinogenic effect of miR-146a and CADM2 in vivo. Results: miR-146a has been shown to promote cell proliferation, migration, and invasion. Here, we found that miR-146a is highly expressed in ccRCC tissues, whereas CADM2 is down-regulated. Hypoxia can induce the expression of miR-146a by stimulating its promoter. In addition, we demonstrated that miR-146a promoted and CADM2 inhibited proliferation, migration, and invasion of ccRCC cells. The 3’ untranslated region (UTR) luciferase reporter assay identified that miR-146a targeted the 3’ UTR of CADM2 and negatively regulated its expression. Ectopic expression of CADM2 counteracted the promoting effect of miR-146a on cell proliferation, migration, invasion, and the epithelial–mesenchymal transition process. Conclusion: Together, the finding of down-regulation of CADM2 by miR-146a can provide new insights into ccRCC pathogenesis and might contribute to the development of novel therapeutic strategies.

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High miR-122 expression promotes malignant phenotypes in ccRCC by targeting occludin

Cited by 30 publications

References 51 publications

Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway

Upregulated lncRNA-UCA1 contributes to metastasis of bile duct carcinoma through regulation of miR-122/CLIC1and activation of the ERK/MAPK signaling pathway

A novel prognostic predictor for clear cell renal cell carcinoma constructed by weighted gene co-expression correlation network analysis

Hypoxia-Regulated miR-146a Targets Cell Adhesion Molecule 2 to Promote Proliferation, Migration, and Invasion of Clear Cell Renal Cell Carcinoma

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