부산대학교 도서관

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.