Downregulation and tumor-suppressive role of XPO5 in hepatocellular carcinoma
- 21 March 2016
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular and Cellular Biochemistry
- Vol. 415 (1-2), 197-205
- https://doi.org/10.1007/s11010-016-2692-3
Abstract
XPO5 (Exp5, Exportin-5) is a transporter protein mainly mediating pre-microRNAs’ nuclear export. Recent studies have demonstrated that XPO5 may play crucial roles in a few of cancers. However, little is known about XPO5 in hepatocellular carcinoma (HCC). In the present study, we elucidated the expression of XPO5 by quantitative real-time PCR (qRT-PCR) and immunohistochemical staining in HCC samples and conducted several functional analyses to address its effects on HCC development. The results demonstrated that both mRNA and protein levels of XPO5 were downregulated in HCC tissues compared to adjacent non-cancerous livers. Ectopic expression of XPO5 significantly suppressed cell proliferation, colony formation, growth in soft agar, and tumorigenicity in nude mice, whereas knockdown of XPO5 by RNA inference showed opposite phenotypes. Moreover, XPO5 knockdown promoted HCC cell migration and decreased the expression of E-cadherin and p53. Additionally, after treatment with DAC and TSA, the mRNA level of XPO5 was upregulated in HCC cells tested, implicating that epigenetic modulation may be involved in the transcription of XPO5. Collectively, our findings suggest that XPO5 functions as a potential tumor suppressor in the development and progression of HCC as well as a promising molecular target for HCC therapy.Keywords
Funding Information
- National Natural Science Foundation of China (CN) (81302064)
- National Natural Science Foundation of China (81472576)
- Shanghai Natural Science Foundation of China (13ZR1434000)
- Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04)
This publication has 28 references indexed in Scilit:
- Single Nucleotide Polymorphisms of MicroRNA Processing Machinery Genes and Outcome of Hepatocellular CarcinomaPLOS ONE, 2014
- MicroRNAs: Synthesis, mechanism, function, and recent clinical trialsBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2010
- Genetic and epigenetic association studies suggest a role of microRNA biogenesis gene exportin-5 (XPO5) in breast tumorigenesis.2010
- A Genetic Defect in Exportin-5 Traps Precursor MicroRNAs in the Nucleus of Cancer CellsCancer Cell, 2010
- Genetic and epigenetic silencing of SCARA5 may contribute to human hepatocellular carcinoma by activating FAK signalingJCI Insight, 2010
- RNA-Regulated Interaction of Transportin-1 and Exportin-5 with the Double-Stranded RNA-Binding Domain Regulates Nucleocytoplasmic Shuttling of ADAR1Molecular and Cellular Biology, 2009
- Dicer, Drosha, and Outcomes in Patients with Ovarian CancerThe New England Journal of Medicine, 2008
- MicroRNAs and cancer: An overviewCell Cycle, 2008
- The Brain-specific Double-stranded RNA-binding Protein Staufen2Online Journal of Public Health Informatics, 2004
- Molecular pathogenesis of human hepatocellular carcinomaNature Genetics, 2002