Open AccessCCND1, NOP14 and DNMT3B are involved in miR‐502‐5p–mediated inhibition of cell migration and proliferation in bladder cancer
Author(s) -
Ying Yufan,
Li Jiangfeng,
Xie Haiyun,
Yan Huaqing,
Jin Ke,
He Liujia,
Ma Xueyou,
Wu Jian,
Xu Xin,
Fang Jiajie,
Wang Xiao,
Zheng Xiangyi,
Liu Ben,
Xie Liping
Publication year - 2020
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12751
Subject(s) - bladder cancer , cancer research , cell growth , downregulation and upregulation , carcinogenesis , dna methylation , cancer , methylation , biology , dnmt3b , flow cytometry , cyclin d1 , epigenetics , microbiology and biotechnology , methyltransferase , cell cycle , gene expression , gene , biochemistry , genetics
Objectives Downregulation of miR‐502‐5p has emerged as a critical factor in tumour progression in several cancers. Herein, we elucidated the role of miR‐502‐5p in bladder cancer. Materials and methods RT‐qPCR was performed to examine the expression of miR‐502‐5p in bladder cancer. And DNA methylation analysis showed that epigenetic mechanisms may contribute to the downregulation of miR‐502‐5p. Then, wound‐healing assay, transwell assay, colony formation assay, CCK8 assay and flow cytometry analysis were applied to evaluate the function of miR‐502‐5p in bladder cancer cell lines. Western blot was conducted to measure the protein levels of related genes. Furthermore, dual‐luciferase reporter assay, in vivo tumorigenesis assay and immunohistochemical staining were also conducted as needed. Results MiR‐502‐5p is frequently downregulated in BCa. Meanwhile, hypermethylation of CpG islands contributes to the downregulation of miR‐502‐5p. Functionally, overexpression of miR‐502‐5p inhibited cell proliferation and migration in vitro and repressed tumour growth in vivo. CCND1, DNMT3B and NOP14 were identified as direct targets of miR‐502‐5p. Interestingly, DNMT3B and miR‐502‐5p established a positive feedback loop in the regulation of bladder cancer. In addition, rescue experiments further validated the direct molecular interaction between miR‐502‐5p and its targets. Conclusions Our study proposed and demonstrated that the miR‐502‐5p–mediated regulatory network is critical in bladder cancer; this network may be useful in the development of more effective therapies against bladder cancer.