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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Biliary Tract Surgery, The First People's Hospital of Foshan, Foshan.
De-Hao
DH
Huang
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou.
Guo-Ying
GY
Wang
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou.
Jian-Wen
JW
Zhang
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou.
Yang
Y
Li
Department of General Surgery and Clinical Laboratory, Zengcheng People's Hospital, (BoJi-Affiliated Hospital of Sun Yat-Sen University), Zengcheng, China.
Xian-Cheng
XC
Zeng
Department of Hepatic Surgery,The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou nanjiang610@163.com.
Nan
N
Jiang
D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D000074749:Deubiquitinating Enzyme CYLD; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D035683:MicroRNAs / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D015854:Up-Regulation
C582676:MIRN501 microRNA, human; D035683:MicroRNAs; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD
CYLD; HCC; miR-501-5p; proliferation