Heterogeneous nuclear ribonucleoprotein K promotes the progression of lung cancer by inhibiting the p53‐dependent signaling pathway

Thoracic Cancer

Ziwei Zhu¹  Le Wang¹  Hao Huang¹  Xingjiu Yang²  Ran Gao²  Mengyuan Li²  Guoxin Zhang²  Wenlong Zhang² 

[1] NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Beijing China;National Human Diseases Animal Model Resource Center, The Institute of Laboratory Animal Science Chinese Academy of Medical Sciences & Peking Union Medical College Beijing China;

关键词: DNA damage response;    hnRNPK;    lung cancer;    p53;   

DOI  :  10.1111/1759-7714.14387

来源: DOAJ

【 摘 要 】

Abstract Background Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is a nucleic acid‐binding protein. Reportedly, hnRNPK is overexpressed in many human tumors, and such overexpression is associated with poor prognosis, implicating the role of hnRNPK as an oncogene during tumorigenesis. In this study, hnRNPK expression in lung cancer tissues was investigated. Methods Briefly, hnRNPK was knocked down in lung cancer cell lines, and effects of knockdown on the cell proliferation, migration, and cell cycle were assessed using a cell counting kit‐8 (CCK‐8) assay, colony formation assay, transwell assay and flow cytometry. The effects of hnRNPK knockdown on the p53‐dependent signaling pathway were examined using western blotting. Finally, the effect of hnRNPK knockdown on tumor growth was verified in vivo using a lung cancer xenograft mouse model. Results hnRNPK knockdown inhibited the cell proliferation, migration and cell cycle. In addition to phenotypic changes, hnRNPK knockdown upregulated expressions of pCHK1, pCHK2, and p53，p21，cyclin D1, thereby mediating the DNA damage response (DDR). The regulatory function of hnRNPK during p53/p21/cyclin D1 signaling in hnRNPK‐knockdown A549 cells was confirmed by suppressed the protein expression of associated signaling pathways, which inhibited DDR. Conclusion hnRNPK plays a crucial role in the progression of lung cancer, ultimately affecting survival rate. Inhibition of progression of lung cancer cells induced by hnRNPK‐knockdown is dependent on activation of p53 by the p53/p21/cyclin D1 pathway.

【 授权许可】

Unknown