TY - JOUR
T1 - Exportin-T promotes tumor proliferation and invasion in hepatocellular carcinoma
AU - Lin, Jianwei
AU - Hou, Yuchen
AU - Huang, Shanzhou
AU - Wang, Ziming
AU - Sun, Chengjun
AU - Wang, Zekang
AU - He, Xiaoshun
AU - Tam, Nga Lei
AU - Wu, Chenglin
AU - Wu, Linwei
N1 - Funding Information:
with XPOT using the data obtained from TCGA. GSEA is supported by the Broad Institute Website (http://software.broadinstitute.org/gsea/ index.jsp).14 Each gene in the list was weighted by its log fold change in expression.
Funding Information:
The Nature Science Foundation of Guangdong Province, China, Grant numbers: 2016A030313242, 2017A030313825; the National Nature Foundation of China, Grant numbers: 81670592, 81601391; The Medical Scientific Research Foundation of Guangdong Province, China, Grant number: A2016033; The Science and Technology Program of Guangzhou, China, Grant number: 201804020075; the Ke Lin programme foundation for youth talents, Grant number: y50181; The Fundamental Research Funds for the Central Universities, Grant number: 17ykjc9; Sanming Project of Medicine in Shenzhen, China, Grant number: SZSM201612075; Shenzhen Healthcare Research Project, Grant number: SZBC2017020
Publisher Copyright:
© 2018 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - bio-marker
KW - cell cycle
KW - exportin-T (XPOT)
KW - hepatocellular carcinoma (HCC)
KW - ubiquitin mediated proteolysis
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U2 - 10.1002/mc.22928
DO - 10.1002/mc.22928
M3 - Article
C2 - 30334580
AN - SCOPUS:85056457532
VL - 58
SP - 293
EP - 304
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 2
ER -