SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer

Autor: Jiazhu Sun, Xueyou Ma, Yufan Ying, Weiyu Wang, Haixiang Shen, Song Wang, Haiyun Xie, Jiahe Yi, Weitao Zhan, Jiangfeng Li, Ben Liu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cell Death Discovery, Vol 8, Iss 1, Pp 1-10 (2022)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-022-01010-8
Popis: Abstract Previous research evidence suggests that microRNAs (miRNAs) play an indispensable role in onset and progression of bladder cancer (BCa). Here, we explored the functions and mechanisms of miR-5581-3p in BCa. miR-5581-3p, as a tumor suppressor in BCa, was detected at a lower expression level in BCa tissue and cells in contrast with the non-malignant bladder tissue and cells. Over-expression of miR-5581-3p remarkably dampened the migration and proliferation of BCa in vitro and in vivo. SMAD3 and FTO were identified as the direct targets of miR-5581-3p by online databases prediction and mRNA-seq, which were further verified. SMAD3 as a star molecule in modulating EMT progress of BCa had been formulated in former studies. Meanwhile, FTO proved as an N6-methyladenosine (m6A) demethylase in decreasing m6A modification was confirmed to regulate the migration and proliferation in BCa. In addition, we conducted rescue experiments and confirmed overexpressing miR-5581-3p partially rescued the effects of the overexpressing SMAD3 and FTO in BCa cells. In conclusion, our studies exhibit that miR-5581-3p is a novel tumor inhibitor of BCa.
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