title: Targeted glypican-3 gene transcription inhibited the proliferation of human hepatoma cells by specific short hairpin RNA.
abstract: Hepatocellular carcinoma (HCC) is a highly chemoresistant cancer with no effective systemic therapy. Despite of surgical or locoregional therapies, prognosis remains poor because of high tumor recurrence or progression, and currently, there are no well-established effective adjuvant therapies. Glypican-3 (GPC-3) is specifically overexpressed in hepatoma and perhaps is a valuable molecular target for HCC therapy. In this present study, the effect of silencing GPC-3 gene transcription on human HepG2 cell proliferation was investigated by constructing GPC-3 short hairpin RNA (shRNA) plasmid. After HepG2 cells were transfected with the most efficient shRNA, GPC-3 mRNA expression (90.4 %) was inhibited significantly and estimated by fluorescence quantitative reverse transcriptase-polymerase chain reaction, and the result was accordance with downregulation at the protein level. The percentage of the cell proliferation was down to 28.9 % in the shRNA group and 19.9 % in the shRNA plus sorafenib group. The cell cycles were arrested in the G1 phase (65.6 %) and the apoptosis rate was increasing (66.75 %) in the shRNA1 group with significant alteration compared with that in the negative-shRNA group. Specific shRNA might intervene effectively GPC-3 activation and inhibit tumor cell proliferation, suggesting that GPC-3 gene should be a potential molecular target for HCC therapy.
authors.affiliation: Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, 20 West Temple Road, Nantong, 226001, Jiangsu Province, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Min
authors.initials: M
authors.lastname: Yao
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.forename: Meijuan
authors.initials: M
authors.lastname: Yan
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Yan
authors.forename: Liwei
authors.initials: L
authors.lastname: Qiu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Wenli
authors.initials: W
authors.lastname: Sai
authors.forename: Dengfu
authors.initials: D
authors.lastname: Yao
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D053673:Glypicans / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D053673:Glypicans; D012333:RNA, Messenger; D034741:RNA, Small Interfering