Enforced expression of miR-101 enhances cisplatin sensitivity in human bladder cancer cells by modulating the cyclooxygenase-2 pathway

Abstract

Abstract. Alterations in microRNA (miRNA) expression have been shown to be involved in the tumor response to chemotherapy. However, the possible role of miR-101 in cisplatin sensitivity in human bladder cancer cells remains unclear. In this study, quantitative polymerase chain reaction and western blotting were utilized to determine the expression profiles of miR-101 and cyclooxygenase-2 (COX-2) in human bladder cancer cells. The effect of miR-101 and small interfering RNA (siRNA) against COX-2 on cell viability was evaluated using MTT assays, and apoptosis levels were determined using fluorescence-activated cell sorting analysis of Annexin V/propidium iodide-stained cells. Luciferase reporter plasmids were constructed to confirm direct targeting. This study found that the expression of miR-101 was downregulated in the cisplatin-resistant cell line T24/CDDP as compared with that in the parental line, T24. Furthermore, overexpression of miR-101 significantly increased the anti-proliferative effects and apoptosis induced by cisplatin, whereas knockdown of miR-101 significantly decreased the anti-proliferative effects and apoptosis induced by cisplatin. In addition, downregulation of miR-101 induced cell survival and cisplatin resistance through the upregulation of COX-2 expression. Luciferase gene reporter assays confirmed that COX-2 was a direct target gene of miR-101. Inhibition of COX-2 using COX-2 siRNA abrogated the cisplatin resistance induced by miR-101 downregulation. These results suggest that miR-101 may provide a novel mechanism for understanding cisplatin resistance in bladder cancer by modulating the COX-2 pathway.

MicroRNA-101 protects cardiac fibroblasts from hypoxia-induced apoptosis via inhibition of the TGF-β signaling pathway

“…More interestingly, miR-101 is known to participate in cellular apoptosis in various cell types. Bu et al (2014) reported that miR-101 enhanced cisplatin-induced apoptosis in human bladder cancer cells by modulating the cyclooxygenase-2 pathway. In addition, a study by Wang et al (2014) demonstrated that miR-101 induced apoptosis in breast cancer cells by targeting Janus Kinase 2.…”

RLIP76-dependent suppression of PI3K/AKT/Bcl-2 pathway by miR-101 induces apoptosis in prostate cancer

“…Recent studies suggested that miR-101 could serve the function of a tumor suppressor gene in various cancers [10,17]. Furthermore, Varambally's work demonstrates that miR-101 expression was somatically lost in 37.5% of clinically localized prostate cancer cells [12].…”

“…The miRNA transfection and Luciferase assay were performed as described previously [17]. Briefly, human prostate cell line DU145 and PC3 were transfected 24 h later using Lipofectamine 2000 according to the manufacturer's instructions (Life technology, USA).…”

Mechanistic Role of MicroRNA in Cancer Chemoprevention by Nonsteroidal Anti-inflammatory Drugs

“…Thereby, any miRNAs that are able to trigger COX-2 may be involved in the COX dependent mechanism of NSAIDs anticancer activity. There are only several studies reporting the inhibition of COX-2 signaling by miRNAs[65-67], but few of them are related to human cancer[67]. A latest study reported that miR-101 was downregulated in the cisplatin-resistant human bladder cancer cells T24/CDDP, while overexpression of miR-101 rescued the anticancer activity of cisplatin.…”

“…A latest study reported that miR-101 was downregulated in the cisplatin-resistant human bladder cancer cells T24/CDDP, while overexpression of miR-101 rescued the anticancer activity of cisplatin. The luciferase reporter assay demonstrated that miR-101 could directly target 3′-UTR of COX-2 gene and silence of COX-2 by siRNAs could simulate the phenotype led by overexpression of miR-101[67]. In addition, a study demonstrated that celecoxib, a COX-2 selective inhibitor, could regulate the expression of miRNA-29c in human gastric cancer cells [68].…”