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Jpn J Clin Oncol. 2015 Aug;45(8):738-44. doi: 10.1093/jjco/hyv063. Epub 2015 Apr 27.

MiR-501-5p regulates CYLD expression and promotes cell proliferation in human hepatocellular carcinoma.

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Department of Biliary Tract Surgery, The First People's Hospital of Foshan, Foshan.
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou.
Department of General Surgery and Clinical Laboratory, Zengcheng People's Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, China.
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou



Previous studies have shown that the micro-ribonucleic acid miR-501-5p is upregulated in hepatocellular carcinoma cells and tissues with high hepatitis B virus replication, and that miR-501 overexpression significantly promotes hepatitis B virus replication. We further analysed a published microarray-based high-throughput dataset (NCBI/GEO/GSE36915) and found that miR-501-5p was upregulated in hepatocellular carcinoma tumour tissues. We therefore investigated the possible function of miR-501-5p during the development of hepatocellular carcinoma.


Expression of miR-501-5p in human hepatocellular carcinoma specimens and cell lines was assessed, using real-time polymerase chain reaction. Luciferase reporter assays were used to confirm CYLD as a target of miR-501-5p. The effect of miR-501-5p on cell proliferation was confirmed, using tetrazolium and colony formation assays. Gene and protein expression were examined, using real-time polymerase chain reaction and western blotting, respectively.


MiR-501-5p was upregulated in hepatocellular carcinoma specimens and cell lines, and directly targeted the 3' untranslated region of CYLD. MiR-501-5p upregulation corresponded with a downregulation of CYLD in the same tissues and cell lines, and overexpression of MiR-501-5p decreased CYLD expression, increased expression of cyclin D1 and c-myc and promoted the proliferation of hepatocellular carcinoma cells in vitro.


This study suggests that miR-501-5p may play an important role in the development of hepatocellular carcinoma by promoting cell proliferation, and indicates that miR-501-5p may represent a novel therapeutic target for hepatocellular carcinoma.


CYLD; HCC; miR-501-5p; proliferation

[Indexed for MEDLINE]

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