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

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.

Keywords: DNA damage response; hnRNPK; lung cancer; p53.