TRIB3 promotes hepatocellular carcinoma growth and predicts poor prognosis

Cancer Biomark. 2020;29(3):307-315. doi: 10.3233/CBM-201577.

Abstract

Background: Tribbles pseudokinase 3 (TRIB3) is a member of the tribbles-related family, which is involved a lot of cellular processes and multiple cancers, such as breast cancer, colorectal cancer, renal cell carcinomas, and lung cancer. However, the expression pattern and biological function of TRIB3 in hepatocellular carcinoma (HCC) has not yet been completely elucidated.

Methods: The expression of TRIB3 and clinicopathological characteristics were evaluated by HCC tissue microarray and qPCR analysis. Lentivirus packaging and transfection were employed to establish cell lines with TRIB3 overexpression or knockdown. The biological functions of TRIB3 in the growth of HCC were determined using MTT and crystal violet assays. Tumor growth was monitored in a xenograft model in vivo.

Results: The expression of TRIB3 was upregulated in HCC tissue samples compared to paired normal tissues in 45 patients examined by qPCR assay. TRIB3 expression was significantly correlated with HCC tumor size and prognosis in postoperative patients by analysis of the TRIB3 expression data and HCC clinical features. Forced expression of TRIB3 significantly promoted HCC growth in vitro. In contrast, downregulation of TRIB3 inhibited cell growth in vitro. Moreover, knockdown of TRIB3 suppressed tumorigenesis of HCC cells in vivo.

Conclusion: TRIB3 promotes growth abilities of HCC cells both in vitro and in vivo and predicts poor prognosis of HCC patients, which serves as a prognostic marker and might provide a potential therapeutic candidate for patients with HCC.

Keywords: TRIB3; growth; hepatocellular carcinoma; prognosis.

Publication types

  • Observational Study

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinogenesis / genetics
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / mortality
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Cell Cycle Proteins / analysis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Prognosis
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Radiotherapy, Adjuvant
  • Repressor Proteins / analysis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Tissue Array Analysis
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • Repressor Proteins
  • TRIB3 protein, human
  • Protein Serine-Threonine Kinases