Neoplasma Vol.69, No.2, p.321–330, 2022
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| Title: miRNA-182-5p promotes human bladder cancer proliferation and migration through the FOXF2/SHH axis |
| Author: Ze Zhang, Chong Wang, Tiantian Liu, Zhao Tang, Rucheng Yan, Chen Zhang, Chao Cheng, Jiawei Wang, Hao Wang, Houbao Huang, Yawei Li |
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Abstract: Increasing evidence suggests that microRNAs (miRNAs) play critical roles in bladder tumorigenesis and development by combining with the 3' untranslated regions (3'-UTRs) of the corresponding mRNAs to negatively regulate gene expression. The role of miR-182-5p in bladder cancer (BC) remains unclear. Therefore, this study aimed to clarify the functional role of miR-182-5p in BC. We predicted candidate mRNAs for miR-182-5p via three databases (TarBase, ENCORI, and miRDB). Dual-luciferase reporter assays and target prediction confirmed FOXF2 as a potential target of miR-182-5p. Quantitative RT-PCR (qRT-PCR) showed that endogenous miR-182-5p expression was significantly upregulated in BC cell lines and clinical samples of BC patients. IHC, western blotting, and qRT-PCR assays indicated that FOXF2 expression was concurrently downregulated in BC tissues and BC cell lines. Gain- and loss-of-function studies showed that the overexpression of miR-182-5p enhanced the proliferation and migration of BC cells, while the downregulation of miR-182-5p showed the opposite results. The effects induced by miR-182-5p were attenuated with the restoration of FOXF2 expression. In BC cells, the upregulation of miR-182-5p not only decreased FOXF2 expression but also markedly increased Sonic hedgehog (SHH) pathway levels. These findings suggested that FOXF2 directly binds to miR-182-5p and that miR-182-5p acts as a tumor promoter in BC genesis and metastasis by targeting FOXF2. In addition, miR-182-5p plays a pro-cancer role by downregulating FOXF2 and activating the SHH pathway.
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| Keywords: miR‐182‐5p; FOXF2; SHH signaling pathway; bladder cancer |
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Published online: 24-Jan-2022
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| Year: 2022, Volume: 69, Issue: 2 |
Page From: 321, Page To: 330 |
doi:10.4149/neo_2021_210903N1266
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