Protective effect of the RNA-binding protein RBM10 in hepatocellular carcinoma

Eur Rev Med Pharmacol Sci. 2020 Jun;24(11):6005-6013. doi: 10.26355/eurrev_202006_21494.

Abstract

Objective: To illustrate the protective effect of RBM10 on hepatocellular carcinoma (HCC) progression and the molecular mechanism.

Patients and methods: RBM10 levels in HCC tissues classified by tumor size and tumor node metastasis (TNM) staging were detected by quantitative real-time polymerase chain reaction (qRT-PCR) Chi-square test was conducted to reveal the relationship between RBM10 level and pathological features in HCC patients. The prognostic potential of RBM10 in HCC was assessed via the Kaplan-Meier method. Overexpression of RBM10 was achieved by transfection of LV-RBM10 in HepG2 and HCC-LM3 cells. Cell counting kit-8 (CCK-8) assay and flow cytometry were carried out to detect viability and apoptosis in HCC cells, respectively. In addition, invasive ability was assessed by transwell assay. Protein level of cleaved-caspase-3 was examined by Western blot. Regulatory effects of RBM10 on protein levels of EGFR, ERK and p-ERK were determined.

Results: RBM10 was downregulated in HCC tissues. Its level was markedly lower in HCC cases with larger tumor size and stage III+IV. Low level of RBM10 predicted poor prognosis in HCC patients. Overexpression of RBM10 suppressed viability and invasiveness in HCC-LM3 and HepG2 cells, but enhanced apoptotic rate and protein level of cleaved-caspase-3. EGFR was upregulated in HCC tissues, which was negatively regulated by RBM10. Overexpression of RBM10 downregulated protein levels of EGFR and p-ERK in HCC-LM3 and HepG2 cells.

Conclusions: RBM10 is downregulated in HCC tissues, which is favorable to the prognosis in HCC patients. As a tumor suppressor, RBM10 attenuates proliferative and invasive abilities, but drives apoptosis in HCC cells, thus alleviating the progression of HCC.

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / metabolism*
  • Cell Proliferation
  • Cells, Cultured
  • Down-Regulation
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism*
  • Male
  • Middle Aged
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction

Substances

  • RBM10 protein, human
  • RNA-Binding Proteins
  • EGFR protein, human
  • ErbB Receptors