miR-31/QKI-5 axis facilitates cell cycle progression of non-small-cell lung cancer cells by interacting and regulating p21 and CDK4/6 expressions.
Cancer Med
; 12(4): 4590-4604, 2023 02.
Article
in En
| MEDLINE
| ID: mdl-36172919
ABSTRACT
BACKGROUND:
RNA-binding protein Quaking-5 (QKI-5), a major isoform of QKIs, inhibits tumor progression in non-small cell lung cancer (NSCLC). However, the underlying molecular mechanisms of QKI-5 in the cell cycle of NSCLC are still largely unknown.METHODS:
MTT, flow cytometry, and colony formation assays were used to investigate cellular phenotypic changes. Mice xenograft model was used to evaluate the antitumor activities of QKI-5. Co-immunoprecipitation, RNA immunoprecipitation (RIP), and RIP sequencing were used to investigate protein-protein interaction and protein-mRNA interaction.RESULTS:
The QKI-5 expression was downregulated in NSCLC tissues compared with that in paired normal adjacent lung tissues. Overexpression of QKI-5 inhibited NSCLC cell proliferative and colony forming ability. In addition, QKI-5 induced cell cycle arrest at G0/G1 phase through upregulating p21Waf1/Cip1 (p21) expression and downregulating cyclin D1, cyclin-dependent kinase 4 (CDK4), and CDK6 expressions. Further analyses showed that QKI-5 interacts with p21 protein and CDK4, CDK6 mRNAs, suggesting a critical function of QKI-5 in cell cycle regulation. In agreement with in vitro study, the mouse xenograft models validated tumor suppressive functions of QKI-5 in vivo through altering cell cycle G1-phase-associated proteins. Moreover, we demonstrated that QKI-5 is a direct target of miR-31. The QKI-5 expression was anticorrelated with the miR-31 expression in NSCLC patient samples.CONCLUSION:
Our results suggest that the miR-31/QKI-5/p21-CDK4-CDK6 axis might have critical functions in the progression of NSCLC, and targeting this axis could serve as a potential therapeutic strategy for NSCLC.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Carcinoma, Non-Small-Cell Lung
/
MicroRNAs
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Lung Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Med
Year:
2023
Document type:
Article
Affiliation country:
China