Background <p>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.</p> Objective <p>We aimed to investigate the role of MMP9 in UBE2C-overexpressed NSCLC progression.</p> Methods <p>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<sup>®</sup> 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.</p> Results <p>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.</p> Conclusions <p>Our findings indicate that UBE2C may be a therapeutic and prognostic target for lung carcinoma.</p>

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

  • Jie Zhao,
  • Juanjuan Dai,
  • Ning Zhou,
  • Dongqin Liu,
  • Dandan Wang,
  • Shuang Miao,
  • Chao Liang,
  • Di An,
  • Jiatong Jiang,
  • Kaikai Gong,
  • Yan Wu

摘要

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.