High expression of TRIM44 is associated with enhanced cell proliferation, migration, invasion, and resistance to doxorubicin in hepatocellular carcinoma

Tumour Biol. 2016 Nov;37(11):14615-14628. doi: 10.1007/s13277-016-5316-3. Epub 2016 Sep 12.

Abstract

Dysregulation of TRIM44 has been reported to be involved in tumorigenesis, but its role in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the clinicopathological and biological significance of TRIM44 in HCC. We found that TRIM44 mRNA and protein expression was upregulated in HCC compared with matched normal tissues. Intriguingly, we also found that TRIM44 expression was significantly correlated with tumor size (P < 0.001), vascular invasion (P < 0.001), intrahepatic metastasis (P < 0.001), distant metastasis (P < 0.001), and Ki-67 expression (P < 0.001). Kaplan-Meier analysis showed that high TRIM44 staining was significantly correlated with shorter overall survival (P < 0.001). TRIM44 was an independent predictor of overall survival in patients with HCC. Furthermore, we found that ectopic expression of TRIM44 could promote cell proliferation via accelerating the G1/S-phase transition in HCC. Moreover, overexpression of TRIM44 could enhance the invasive and migratory capacity of HCC cells. Meanwhile, we found that high expression of TRIM44 could enhance resistance of HCC cells to doxorubicin via accelerating NF-κB activation. In conclusion, our results suggest that TRIM44 may be a novel prognostic indicator and potential therapeutic target of HCC.

Keywords: Cell proliferation; Drug resistance; Hepatocellular carcinoma (HCC); Invasion; Migration; TRIM44.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Blotting, Western
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / secondary*
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation*
  • Doxorubicin
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoenzyme Techniques
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Tripartite Motif Proteins
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • TRIM44 protein, human
  • Tripartite Motif Proteins
  • Doxorubicin