There is increasing evidence suggesting that dysregulation of some microRNAs (miRNAs) may contribute to tumor progression and metastasis and have been proposed to be key regulators of diverse biological processes such as transcriptional regulation, cell growth and tumorigenesis. Previous studies have shown that miR-137 is dysregulated in some malignancies, but its role in bladder cancer is still unknown. In our study, we find that miR-137 is up-regulated in human bladder cancer tissues and cell lines. Moreover, the higher level of miR-137 was associated with pM or pTNM stage in clinical bladder cancer patients. Enforced expression of miR-137 in bladder cancer cells significantly enhanced their proliferation, migration and invasion. Bioinformatics analysis identified the tumor suppressor gene PAQR3 as a potential miR-137 target gene. Further studies indicated that miR-137 suppressed the expression of PAQR3 by binding to its 3′-untranslated region. Silencing of PAQR3 by small interfering RNAs phenocopied the effects of miR-137 overexpression, whereas restoration of PAQR3 in bladder cancer cells bladder cancer cells overexpressing miR-137, partially reversed the suppressive effects of miR-137. These findings indicate that miR-137 could be a potential oncogene in bladder cancer.

Abstract. Long non-coding RNAs (lncRNAs) are important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation and survival. Alterations in the function of lncRNAs promote tumor formation, progression and metastasis. The purpose of the present study was to identify novel tumor suppressor lncRNAs, and elucidate their physiological function and mechanism in renal cell carcinoma (RCC). The results of the present study revealed that the expression of the lncRNA, TRIM52-AS1, was downregulated in RCC, which was demonstrated using reverse transcription-quantitative polymerase chain reaction analysis. Furthermore, the effects of TRIM52-AS1 on proliferation, cell migration and apoptosis were analyzed using a wound scratch assay, a 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometric analysis, respectively. The overexpression of TRIM52-AS1 using a synthesized vector significantly suppressed cell migration and proliferation, and induced apoptosis of the RCC cells in vitro, and interference of its expression led to the opposite effects. The present study was the first, to the best of our knowledge, to demonstrate that TRIM52-AS1 functions as a tumor suppressor in RCC. Further investigation is required to elucidate the molecular mechanisms underlying the effects of TRIM52-AS1 in the development of RCC.

Circular RNAs (circRNAs) are non-coding RNAs that are connected at the 3' and 5' ends by an exon or intron. Studies increasingly show that circRNAs play an important role in tumorigenesis by acting as a 'sponge' for microRNAs (miRNAs), which abrogates the latter's effect on their target mRNAs. To identify a possible circRNA/miRNA/mRNA network in bladder cancer (BCa), we analyzed the circRNA and mRNA expression profiles of BCa and adjacent normal bladder tissues. A total of 127 circRNAs and 1,612 mRNAs were differentially expressed in the tumor tissues, and were primarily associated with cancer-related pathways. A competing endogenous RNAs (ceRNA) network was then constructed which predicted a regulatory axis of circRNA_0071196, miRNA-19b-3p and its target gene citron Rho-interacting serine/threonine kinase (CIT). Luciferase reporter assay validated the relationship between circRNA_0071196 and miRNA-19b-3p and of the latter with CIT. Furthermore, CIT was overexpressed in the BCa tissues, and was found to be correlated with metastasis and tumor histological grade. Knockdown of CIT in the human bladder cancer cell line 5367 significantly inhibited the proliferation, migration and colony formation capacity of the cells, and also upregulated the mediators of the p53 and RhoA-ROCK signaling cascades that regulate cell cycle and migration. Taken together, our findings indicate that circRNA-0071196 upregulates CIT levels in BCa by sponging off miRNA-19b-3p, and the circRNA_0071196/miRNA-19b-3p/CIT axis is a potential therapeutic target in BCa.

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Background: Clear cell renal cell carcinoma (ccRCC) is a malignancy with a high incidence rate and poor prognosis worldwide. Copper ionophore–induced death (CID) plays an important role in cancer progression.Methods: One training and three validation datasets were acquired from TCGA, GEO and ArrayExpress. K-means clustering was conducted to identify the CID subtypes. The ESTIMATE and CIBERSORT algorithms were employed to illustrate the immune microenvironment of ccRCC. LASSO Cox regression was applied to construct the CID feature-based prognostic model. The immunotherapy cohort was acquired from the literature to explore the potential risk scores for predicting immunotherapy responsiveness.Results: Two CID-related cancer subtypes of ccRCC were identified that performed different immune microenvironment characteristics and prognosis. Based on the identified subtypes, we analyzed the biological heterogeneity and constructed a gene prognostic model. The prognostic model performed well in one training dataset, three validation datasets, and different clinical pathological groups. The prognostic model has a good potential for predicting cancer immune features and immunotherapy responsiveness.Conclusion: CID plays an important role in the tumor microenvironment progression of ccRCC. The robust gene prognostic model developed can help predict cancer prognosis, immune features, and immunotherapy responsiveness.