MicroRNA-374a Inhibits Aggressive Tumor Biological Behavior in Bladder Carcinoma by Suppressing Wnt/β-Catenin Signaling

Abstract

Background/Aims: microRNA (miR)-374a plays a crucial role in cancer progression by promoting the metastasis and proliferation of various types of malignant tumors. Because its role in bladder cancer is unknown, we investigated whether miR-374a affects the progression of bladder cancer and studied the underlying mechanism. Methods: The Cancer Genome Atlas was used to analyze the clinical relevance of miR-374a. Quantitative PCR, western blotting, and luciferase and immunofluorescence assays were used to detect the expression patterns, downstream targets, and function of miR-374a in bladder cancer cells. Apoptosis was evaluated by flow cytometry after cisplatin treatment. Results: Via in silico analysis, low levels of miR-374a were associated with poor prognosis in bladder cancer patients with distant metastasis. WNT5A was a direct target of miR-374a in two bladder cancer cell lines. miR-374a mimic abrogated the metastatic potential and invasiveness of bladder cancer cells via WNT5A downregulation in both T24 and TCCSUP human bladder cancer cells; the opposite was observed with miR-374a inhibitor. In addition, miR-374a treatment reduced the phosphorylation and nuclear translocation of β-catenin. Cisplatin treatment significantly increased the apoptosis rate. Expression levels of cancer stemness-related proteins were reduced in miR-374a mimic-pretreated cells. Conclusion: Lower expression of miR-374a is associated with poor prognosis and miR-374a improves tumor biological behavior in bladder cancer cells, suggesting that miR-374a might be a novel small-molecule therapeutic target.

miRNA-641 inhibits the proliferation, migration, and invasion and induces apoptosis of cervical cancer cells by directly targeting <em>ZEB1</em>

“…More than 2,500 miRNAs have been validated in the human genome 10. Recently, miRNAs were found to be dysregulated in most human cancer types, such as lung cancer,11 colorectal cancer,12 breast cancer,13 and bladder cancer 14. Particularly, a variety of miRNAs are aberrantly expressed in cervical cancer 15.…”

Emerging Roles of Cancer Stem Cells in Bladder Cancer Progression, Tumorigenesis, and Resistance to Chemotherapy: A Potential Therapeutic Target for Bladder Cancer

“…A recent study also showed that in BC, direct targeting of WNT5A by miR-374a treatment inhibited the phosphorylation and nuclear translocation of β-catenin, thus decreasing the expression of BC stemness-related proteins and the aggressiveness behavior of BC [124]. Other miRNAs which inhibit bladder CSCs proliferation, self-renewal, and metastasis are miR-139-5p (by targeting the Bmi1 oncogene [125]), miR-379-5p (by targeting MDM2 [126]), miR-125a-5p (by targeting FUT4 [127]), and miR-24 (by targeting CARMA3 [128]), suggesting that miRNAs could become a novel small-molecule therapeutic target for urothelial carcinoma.…”

Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

“…The particular miRNAs in this paper are associated with cancer occurrence, metastasis and invasion. Indeed, miR-145, miR-202 and miR-374 has been proposed as diagnostic, prognostic or therapeutic marker of BLCA [45,46] .miR-202 and miR-347 participate in invasion, metastasis and cancer progression [46,47], while miR-145 modulates suppressor of cytokine signaling 7 (socs7) to enhance IFN-β expression, thus contributing to BLCA apoptosis. We speculate that deregulation of these miRNAs would be in consistence with the phenotype of POLR2K overexpression in BLCA, which should be further veri ed by experiments.…”