MiR-20a-5p Negatively Regulates NR4A3 to Promote Metastasis in Bladder Cancer.

Zhao Chen,Wei Long Zhong,Haibei Yang,Zhiming Liu

doi:10.1155/2021/1377989

Abstract

Metastasis is the leading cause of death in cancer patients. Therefore, the prediction and treatment of metastasis are critical in improving the survival of patients with bladder cancer. In this study, we aimed to investigate the role of miR-20a-5p and NR4A3 in bladder cancer and the regulatory relationship between them. The high expression of miR-20a-5p in the bladder cancer (BCa) tissues and cells was determined by qRT-PCR. Exogenous miR-20a-5p overexpression promoted the proliferation, migration, and invasion of BCa cells. MiR-20a-5p inhibition inhibited the BCa cell proliferation, invasion, and migration. NR4A3 was proved to be the target gene of miR-20a-5p by the double luciferase reporter assay. In addition, the reduction of NR4A3 could promote the proliferation, invasion, and clonal formation of the bladder cancer cells 5637 and T24. NR4A3 overexpression could reverse the carcinogenic effect of miR-20a. We further confirmed that the oncogenic effect of miR-20a was achieved by promoting EMT in tumor cells. MiR-20a-5p promoted the growth and metastasis of the bladder cancer cells by inhibiting the expression of the tumor suppressor gene NR4A3 and played a carcinogenic role in BCa. Thus, miR-20a-5p may become a potential therapeutic target for BCa treatment.

Highlights

Bladder cancer is the most common tumor of the urinary system, and its morbidity and mortality rank first [1,2,3,4]
MiR-20a-5p Was Upregulated in Bladder Cancer Tissues
To investigate the role of miR-20a-5p in bladder cancer, we collected 30 cases of bladder cancer tissues and paracancer control tissues that had been surgically removed. e expression of miR-20a-5p in bladder cancer and adjacent tissues was detected by qPCR. e experimental results showed that miR-20a-5p expression level in bladder cancer tissues was significantly higher than in adjacent control tissues (Figure 1(a))

Summary

Introduction

Bladder cancer is the most common tumor of the urinary system, and its morbidity and mortality rank first [1,2,3,4]. Erefore, bladder tumor metastasis often occurs in many diagnosed patients, resulting in a poor prognosis [7, 8]. Specific miRNAs with an abnormal expression in the bladder are closely related to the occurrence and development of bladder cancer and may be a new target for the treatment of bladder cancer. MiRNA is a noncoding small molecule RNA with a length of approximately 19 to 25 nucleotides. It is highly conserved, sequential, and tissue-cell specific in the eukaryotes. Recent studies have shown that mature miRNAs can complement and pair with the 3′UTR of the target mRNA using the “seed region” (2 to 7 nucleotides) and bind to the 5′UTR or ORF, thereby playing a regulatory role [13]

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