UBE2C regulating the lung carcinoma progression via inhibiting ubiquitin-proteasomal degradation to increase MMP9 protein stability.

Abstract

Background: Non-small-cell-lung-cancer (NSCLC) is a prevalent lung malignancy among humans. UBE2C is a critical component of the ubiquitin-proteasome system, and its expression level is significantly associated with cancer development and cell proliferation. Nevertheless, the mechanisms of UBE2C in NSCLC remain unclear.

Objective: We aimed to investigate the role of MMP9 in UBE2C-overexpressed NSCLC progression.

Methods: The GEPIA database and Kaplan-Meier curves were used to determine UBE2C expression in human tumors and survival in NSCLC. CCK8, colony formation, and Transwell^® assays were employed to assess the function of UBE2C in vitro. Western blotting, immunofluorescence assay, and RT-qPCR were utilized to determine protein and mRNA expression levels. CHX chase and co-immunoprecipitation assays were used to elucidate the regulatory mechanism.

Results: This research proved that UBE2C expression was related to patient overall survival, cell proliferation and migration. Furthermore, overexpressed UBE2C could promote the protein stability of Matrix metalloproteinase-9 (MMP9) to upregulate its protein level in NSCLC cells. Meanwhile, UBE2C upregulation promoted lung carcinoma progression by modulating MMP9 expression.

Conclusions: Our findings indicate that UBE2C may be a therapeutic and prognostic target for lung carcinoma.