MicroRNA-101 inhibits cell migration and invasion in bladder cancer via targeting FZD4

Exp Ther Med. 2019 Feb;17(2):1476-1485. doi: 10.3892/etm.2018.7084. Epub 2018 Dec 11.

Abstract

Dysfunction of microRNAs (miRs) has been implicated in the development and progression of various human cancers. Our previous study demonstrated that miR-101 inhibited bladder cancer cell proliferation and invasion through inhibition of c-FOS expression. As an miR generally has many targets, other targets of miR-101 may also serve important roles in bladder cancer progression. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to examine mRNA and protein expression, respectively. Wound healing and Transwell assays were conducted to study cell migration and invasion, respectively. The luciferase reporter gene assay was performed to verify one of the targets of miR-101. The data in the present study indicate that the expression of miR-101 is significantly reduced in bladder cancer tissues compared with that in adjacent non-tumour tissues. In addition, miR-101 expression is also downregulated in bladder cancer cell lines compared with that in normal bladder epithelial cells. Furthermore, low expression of miR-101 was significantly associated with tumour metastasis, advanced clinical stage, and poor prognosis in bladder cancer. Frizzled class receptor 4 (FZD4) was identified as a novel target of miR-101 in bladder cancer cells. The expression of FZD4 was significantly upregulated in bladder cancer tissues and cell lines. Both miR-101 overexpression and FZD4 inhibition caused a significant reduction of the migration and invasion of bladder cancer cells, whereas overexpression of FZD4 reversed the suppressive effects of miR-101 on bladder cancer cell migration and invasion. In conclusion, it was demonstrated that miR-101 downregulation is associated with bladder cancer progression and that miR-101 can inhibit bladder cancer cell migration and invasion via directly targeting FZD4. The present study expands the understanding of the molecular mechanisms underlying bladder cancer progression.

Keywords: bladder cancer; frizzled class receptor 4; invasion; microRNA; migration.