title: MicroRNA-21 suppresses PTEN and hSulf-1 expression and promotes hepatocellular carcinoma progression through AKT/ERK pathways.
abstract: MicroRNAs (miRNAs) have been believed to associate with malignant progression including cancer cell proliferation, apoptosis, differentiation, angiogenesis, invasion and metastasis. However, the functions of miRNAs are intricate, one miRNA can directly or indirectly target multiple genes and function as oncogene or tumor suppressor gene. In this study, we found that miR-21 inhibits PTEN and human sulfatase-1 (hSulf-1) expression in hepatocellular carcinoma (HCC) cells. The hSulf-1 is a heparin-degrading endosulfatase, which can inhibit the heparin binding growth factor-mediated signaling transduction into cells. Therefore, miR-21-mediated suppression of both hSulf-1 and PTEN led to activation of AKT/ERK pathways and epithelial-mesenchymal transition (EMT) in HCC cells, and finally enhance the activity of HCC cell proliferation and movement and promote HCC xenograft tumor growth in mouse models. These findings may provide candidate targets for prevention and treatment of HCC.
authors.affiliation: Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & Institute, Second Military Medical University, Shanghai 200438, China.
authors.forename: Longlong
authors.initials: L
authors.lastname: Bao
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.forename: Can
authors.initials: C
authors.lastname: Xu
authors.forename: Weidan
authors.initials: W
authors.lastname: Ji
authors.forename: Shuwen
authors.initials: S
authors.lastname: Shen
authors.forename: Gaoya
authors.initials: G
authors.lastname: Xu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zeng
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Haihua
authors.initials: H
authors.lastname: Qian
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Mengchao
authors.initials: M
authors.lastname: Wu
authors.forename: Changqing
authors.initials: C
authors.lastname: Su
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D015238:Sulfotransferases / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; C470791:SULF1 protein, human; D015238:Sulfotransferases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: AKT; EMT; ERK; Epithelial–mesenchymal transition; HCC; HSPG; Hepatocellular carcinoma; Human sulfatase-1; MicroRNA; PI3K-protein kinase B; Signaling; epithelial–mesenchymal transition; extracellular signal regulated kinase; hSulf-1; heparan sulfate proteoglycans; hepatocellular carcinoma; human sulfatase-1; qRT-PCR; quantitative reverse transcription-polymerase chain reaction