Anti-invasion and anti-migration effects of miR-199a-3p in hepatocellular carcinoma are due in part to targeting CD151.
Several studies have reported reduced miR-199a-3p expression in hepatocellular carcinoma (HCC). In an effort to discover important target genes for miR-199a-3p that may be related to HCC development or progression, we identified the tetraspanin, transmembrane glycoprotein CD151. Luciferase reporter assays and western blotting identified CD151 as a bona fide miR-199a-3p target gene. While CD151 protein was increased in the mesenchymal but not the epithelial HCC cell lines, CD151 knockdown with siRNA did not reduce HCC cell proliferation in either group of cells. miR-199a-3p reduced in vitro invasion and migration of CD151-positive HCC cells. Examination of the mRNA and protein expression in pairs of primary HCC tumors and adjacent benign tissues showed that not only was CD151 mRNA and protein increased in the tumors but also that an inverse correlation exists between the miR-199a-3p and CD151 RNA expression. We report that CD151 is a target of miR-199a-3p and that increased CD151 protein resulting from reduced miR-199a-3p could contribute to the development of metastatic HCC.
College of Pharmacy, Ohio State University, Columbus, OH, USA.
Ji Hye
JH
Kim
College of Pharmacy, Ohio State University, Columbus, OH, USA.
Mohamed
M
Badawi
College of Pharmacy, Ohio State University, Columbus, OH, USA.
Jong-Kook
JK
Park
College of Pharmacy, Ohio State University, Columbus, OH, USA.
Jinmai
J
Jiang
Department of Biostatistics, Ohio State University, Columbus, OH, USA.
Xiaokui
X
Mo
Divisions of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA.
Lewis R
LR
Roberts
College of Pharmacy, Ohio State University, Columbus, OH, USA.
Thomas D
TD
Schmittgen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D008099:Liver / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D060185:Tetraspanin 24 / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D035683:MicroRNAs; D060185:Tetraspanin 24; C531408:mirn199 microRNA, human