Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma

Jianwei Lin, Yuchen Hou, Shanzhou Huang, Ziming Wang, Chengjun Sun, Zekang Wang, Xiaoshun He, Nga Lei Tam, Chenglin Wu, Linwei Wu

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Exportin-T (XPOT) belongs to the RAN-GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up-regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expression of XPOT in HCC indicated worse prognosis via bioinformatics analysis. Consistently, immunohistochemical staining of 95 pairs of tumors and adjacent normal liver tissues (ANLT) also showed up-regulation of XPOT. Small interfering (si) RNA transfection was used to down-regulate XPOT in HepG2 and 7721 cell lines. Cell Counting Kit-8 (CCK8) assays were performed to analyze cell proliferation. Cell migration and invasion were measured by scratch wound healing assays and migration assays. Subcutaneous xenograft models were using to explore the role of XPOT in tumor formation in vivo. Down-regulation of XPOT significantly inhibited tumor proliferation and invasion in vitro and vivo. Gene set enrichment analysis (GSEA) results indicated that XPOT may affect tumor progression through cell cycle and ubiquitin-mediated proteolysis. Furthermore, knockdown of XPOT caused a block in G0/G1 phase as evidenced by down-regulation of cyclin-dependent kinase 1 (CDK1), cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase 4 (CDK4), CyclinA1 (CCNA1), CyclinB1 (CCNB1), CyclinB2 (CCNB2), and CyclinE2 (CCNE2) in HCC cells. In conclusion, our findings indicate that XPOT could serve as a novel biomarker for prognoses and a potential therapeutic target for patients with HCC.

Original languageEnglish (US)
Pages (from-to)293-304
Number of pages12
JournalMolecular Carcinogenesis
Volume58
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • bio-marker
  • cell cycle
  • exportin-T (XPOT)
  • hepatocellular carcinoma (HCC)
  • ubiquitin mediated proteolysis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma'. Together they form a unique fingerprint.

Cite this