Tumor suppressive functions of hsamiR34a on cell cycle, migration and protective autophagy in bladder cancer.
Int J Oncol
; 62(5)2023 May.
Article
em En
| MEDLINE
| ID: mdl-37083075
ABSTRACT
Bladder cancer (BC) cells exhibit a high basal level of autophagy activity, which contributes to the development of a protective mechanism for cellular survival against current treatments. HsamicroRNA34a (miR34a) presents antitumor function in several types of cancer. However, the functional mechanism of miR34a in regulating tumor aggressiveness and protective autophagy of BC remains largely unknown. First, transfected BC cells with miR34a mimic exhibited LC3II and p62 accumulation through immunofluorescence staining. It was demonstrated that syntaxin 17 (STX17), which is required for autophagosomelysosome fusion, was downregulated upon miR34a mimic treatment. Mechanistically, miR34a reduced the expression of STX17 proteins that directly bind on STX17 3'untranslated regions and thus suppressed STX17 mRNA translation to eventually inhibit protective autophagy in BC. Cell viability and colony formation assays revealed that overexpression of miR34a in BC cells enhances the chemosensitivity of cisplatin, doxorubicin, epirubicin and mitomycin C. Furthermore, miR34a inhibited cell proliferation and triggered G0/G1 cell cycle arrest by inhibiting cyclin D1 and cyclin E2 protein expression. Moreover, miR34a suppressed cell motility through the downregulation of epithelialmesenchymal transition. In summary, miR34a inhibits cell proliferation, motility and autophagy activity in BC, which can benefit BC treatment.
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
MicroRNAs
Limite:
Humans
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2023
Tipo de documento:
Article