NUP62 promotes non-small cell lung cancer progression by enhancing STAT4 nuclear translocation to upregulate CFH transcription.

Globally, non-small cell lung cancer (NSCLC) accounts for a substantial proportion of cancer deaths. Nucleoporin 62 (NUP62), a key component of the nuclear pore complex, is tightly linked to cellular functions and tumorigenesis. This study demonstrated that NUP62 was significantly overexpressed in NSCLC tissues. Preliminary investigation conducted via the Kaplan-Meier Plotter database suggested that such aberrant overexpression correlates with poor clinical outcomes in NSCLC cases. For the purpose of studying the loss- and gain-of-function characteristics of NUP62 among NSCLC cell lines, we established NUP62-overexpressing and NUP62-knockdown cell lines using lentivirus-mediated gene delivery and RNA interference, respectively. Further experiments revealed that NUP62 overexpression elevated NSCLC cell proliferation, migration, and invasion capabilities, while NUP62 knockdown attenuated these malignant phenotypes. Mechanistically, upon phosphorylation, signal transducer and activator of transcription 4 (STAT4) migrates into the nucleus and modulates gene expression. STAT4 is also a transcription factor for complement factor H (CFH), which enables cancer cells to evade complement-mediated immune attack. In this study, NUP62 overexpression dramatically increased phosphorylated STAT4 (p-STAT4) in the nucleus, thus upregulating the transcription of CFH. Rescue assays uncovered that although increased STAT4 expression enhanced proliferative, migratory and invasive abilities of NSCLC cells, such malignant properties could be notably abolished by NUP62 depletion. In conclusion, abrogating of the NUP62-STAT4-CFH axis diminishes the neoplastic phenotypes of NSCLC cells. This finding supplies reliable molecular evidence for drug target screening and clinical prognosis evaluation of NSCLC.