MicroRNA165p/BIMP1/NFκB axis regulates autophagy to exert a tumorsuppressive effect on bladder cancer.
Mol Med Rep
; 24(2)2021 Aug.
Article
em En
| MEDLINE
| ID: mdl-34132358
ABSTRACT
Bladder cancer (BC) is the second most common urological disease worldwide. Previous studies have reported that microRNA (miR)165p is associated with the development of BC, but whether miR165p regulates BC cell autophagy remains unknown. Thus, the aim of the present study was to investigate this issue. miR165p expression in BC cells was assessed by reverse transcriptionquantitative PCR. Cell viability and apoptosis were detected via Cell Counting Kit8 and flow cytometry assays, respectively. For cell autophagy detection, autophagic flux was detected using a mCherrygreen fluorescent proteinmicrotubuleassociated proteins 1A/1B light chain 3B (LC3) puncta formation assay, followed by determination of autophagyrelated protein markers. The targeting relationship between miR165p and caspase recruitment domain family member 10 (BIMP1) was confirmed using a dualluciferase reporter assay, followed by detection of the BIMP1/NFκB signaling pathway. The results showed that miR165p overexpression inhibited cell viability, whereas miR165p knockdown promoted cell viability in BC. Furthermore, miR165p overexpression induced autophagy, which was accompanied by increased autophagic flux and expression of the autophagyrelated proteins LC3II and beclin 1, as well as decreased p62 expression, whereas miR165p silencing led to an inhibition of autophagy in BC cells. Moreover, autophagy inhibitor 3methyladenine treatment inhibited cell autophagy and apoptosis in miR165poverexpressing cells. Mechanistic studies demonstrated that miR165p could inhibit the BIMP1/NFκB signaling pathway and this inhibition was achieved by directly targeting BIMP1. Furthermore, it was found that blockade of the BIMP1/NFκB signaling pathway inversed the inhibitory effects of miR165p knockdown on autophagy in BC cells. In vivo experiments further verified the tumorsuppressive effect on BC of the miR165p/BIMP1/NFκB axis. Therefore, the results of the present study indicated that miR165p promotes autophagy of BC cells via the BIMP1/NFκB signaling pathway, and an improved understanding of miR165p function may provide therapeutic targets for clinical intervention in this disease.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Neoplasias da Bexiga Urinária
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Transdução de Sinais
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Regulação Neoplásica da Expressão Gênica
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MicroRNAs
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Proteínas Relacionadas à Autofagia
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2021
Tipo de documento:
Article