title: MiR-20a Induces Cell Radioresistance by Activating the PTEN/PI3K/Akt Signaling Pathway in Hepatocellular Carcinoma.
abstract: OBJECTIVE
  To investigate the role of miR-20a in hepatocellular carcinoma (HCC) cell radioresistance, which may reveal potential strategies to improve treatment.
  
  
  METHODS
  The expression of miR-20a and PTEN were detected in HCC cell lines and paired primary tissues by quantitative real-time polymerase chain reaction. Cell radiation combined with colony formation assays was administrated to discover the effect of miR-20a on radiosensitivity. Bioinformatics prediction and luciferase assay were used to identify the target of miR-20a. The phosphatidylinositol 3-kinase inhibitor LY294002 was used to inhibit phosphorylation of Akt, to verify whether miR-20a affects HCC cell radioresistance through activating the PTEN/PI3K/Akt pathway.
  
  
  RESULTS
  MiR-20a levels were increased in HCC cell lines and tissues, whereas PTEN was inversely correlated with it. Overexpression of miR-20a in Bel-7402 and SMMC-7721 cells enhances their resistance to the effect of ionizing radiation, and the inhibition of miR-20a in HCCLM3 and QGY-7701 cells sensitizes them to it. PTEN was identified as a direct functional target of miR-20a for the induction of radioresistance. Overexpression of miR-20a activated the PTEN/PI3K/Akt signaling pathway. Additionally, the kinase inhibitor LY294002 could reverse the effect of miR-20a-induced radioresistance.
  
  
  CONCLUSIONS
  MiR-20a induces HCC cell radioresistance by activating the PTEN/PI3K/Akt pathway, which suggests that miR-20a/PTEN/PI3K/Akt might represent a target of investigation for developing effective therapeutic strategies against HCC.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Yuqin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong Province, China; Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Tongxin
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Radiation Oncology, Cancer Hospital, Hangzhou, Zhejiang Province, China.
authors.forename: Quanquan
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Radiation Oncology, Nanhai Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
authors.forename: Shunli
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: wangwei9500@hotmail.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address: chenlhsmu@126.com.
authors.forename: Longhua
authors.initials: L
authors.lastname: Chen
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000532:radiotherapy*; D008156:Luciferases / Q000032:analysis; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009025:Morpholines / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012334:RNA, Neoplasm / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011836:Radiation Tolerance; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014410:Tumor Stem Cell Assay
chemical_list: D002867:Chromones; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D009025:Morpholines; D009363:Neoplasm Proteins; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012334:RNA, Neoplasm; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D008156:Luciferases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human