title: Hypoxia-inducible MiR-182 promotes angiogenesis by targeting RASA1 in hepatocellular carcinoma.
abstract: BACKGROUND
  Hypoxia is a common feature of solid tumors, including HCC. And hypoxia has been reported to play an important role in HCC progression. However, the potential mechanism of miRNAs in hypoxia mediating HCC progression still remains unclear.
  
  
  METHODS
  The HCC cells were cultured in the atmosphere of 1 % oxygen to induce hypoxia. The microRNA microarray was employed to search for the hypoxia-inducible miRNAs. RT-PCR, western blot and immunohistochemistry were used to detect the RNA and protein levels. HUVEC were applied to explore the angiogenesis level.
  
  
  RESULTS
  We found that miR-182 was upregulated in the hypoxia-based microarray. We then revealed that miR-182 was also significantly increased in the HCC tissues compared to the corresponding normal tissues. In vitro capilliary tube formation assays showed that the miR-182 promoted angiogenesis. RASA1 was demonstrated as the direct target of miR-182. In addition, the suppression of RASA1 phenocopied the pro-angiogenesis effects of miR-182. Besides, RASA1 was also decreased in the hypoxia HCC cells while the inhibition of miR-182 partially restored the level of RASA1.
  
  
  CONCLUSIONS
  Our data showed that hypoxia regulated the expression of miR-182 and RASA1 to promote HCC angiogenesis.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Chengli
authors.initials: C
authors.lastname: Du
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Wendi
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Ding
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Owusu-Anash K
authors.initials: OA
authors.lastname: Gyabaah
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. drwujian@hotmail.com.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. drwujian@hotmail.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. shusenzheng@zju.edu.cn.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D046228:Microarray Analysis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D020729:p120 GTPase Activating Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C538984:Mirn182 microRNA, human; C557248:RASA1 protein, human; D020729:p120 GTPase Activating Protein