Long non-coding RNA MEG3 suppresses the development of bladder urothelial carcinoma by regulating miR-96 and TPM1

Abstract

We aimed at investigating effects of long non-coding RNA maternally expressed 3 (MEG3) on the proliferation, cell cycle and apoptosis of bladder urothelial carcinoma cells and regulatory relationships among lncRNA MEG3, miR-96 and α-tropomyosin 1 (TPM1). Human clinical data from The Cancer Genome Atlas (TCGA) which contains bladder urothelial carcinoma tissues and adjacent tissues were used for analysis. The expression profiles of MEG3, miR-96, TPM1, cell cycle-related genes and apoptosis-related genes were examined by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Regulating relationship among MEG3, miR-96 and TPM1 was confirmed by dual luciferase reporter assay. MTT assay and flow cytometry were performed to observe cell proliferation, cell cycle and apoptosis. The effects of lncRNA MEG3 on bladder urothelial carcinoma were confirmed both in vivo and in vitro. The mRNA expression and protein expression of MEG3, TPM1 were down-regulated in carcinoma tissues, whereas miR-96 expression was up-regulated. MEG3 overexpression resulted in miR-96 downregulation along with TPM1 upregulation, which inhibited cell proliferation and cell cycle but promoted cell apoptosis of bladder urothelial carcinoma cells in vitro, and at the same time inhibited tumor growth in vivo. In this process, expressions of apoptosis-related protein BCL2 associated X (Bax), cleaved-caspase 3 was up-regulated, whereas apoptosis regulator protein (Bcl-2) expression was suppressed when MEG3 was overexpressed, and cell cycle-related protein Cyclin D1 was down-regulated. LncRNA MEG3 low-expression promotes the proliferation and inhibits apoptosis of bladder urothelial carcinoma cells by regulating miR-96 along with TPM1. ARTICLE HISTORY

DANCR promotes HCC progression and regulates EMT by sponging miR‐27a‐3p via ROCK1/LIMK1/COFILIN1 pathway

“…For instance, SNHG5 regulates GSK3‐β expression by competitively binding miR‐26a‐5p in HCC . MEG3 inhibits proliferation and promotes apoptosis of bladder urothelial carcinoma cells by decoying miR‐96 and then indirectly regulates TPM1 . In our study, we demonstrated that DANCR acted as a competing endogenous RNA of miR‐27a‐3p to regulate LIMK1 expression in HCC development.…”

Identification of Key Biomarkers in Bladder Cancer: Evidence from a Bioinformatics Analysis

“…In contrast, high expression of TPM1, CASQ2, and CRYAB was correlated with poor survival, while high expression of CASA2 and CRYAB was correlated with poor DFS. In a recent study, Liu et al showed that upregulation of TPM1 and miR-96 by lncRNA MEG3 in bladder cancer cells inhibited cell proliferation, induced apoptosis in vitro, and inhibited tumor growth in a xenograft mouse model, supporting our idea of TPM1 as tumor suppressor [55]. Additionally, Thorsen et al revealed that the mRNA expression level and protein expression level of TPM1 were downregulated in BCa [56].…”

Overexpression of long noncoding RNA GAS5 suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mTOR pathway

“…In our study, our results showed that miRNA-106a-5p was significantly upregulated in GC tissues and cells. In recent years a growing number of reports have shown that the disorders of competitive endogenous RNA (ceRNA) networks tend to result in carcinogenesis via tumor suppressors and oncogenes through their ceRNA function (Cardoso et al, 2018; Liu et al, 2018; Zhang et al, 2018). Nonetheless, the ceRNA hypothesis has provided a novel viewpoint to explore disease processes by regulating ceRNA networks through miRNA competition or sponge for cancer therapy.…”