title: ANT2 suppression by shRNA may be able to exert anticancer effects in             HCC further by restoring SOCS1 expression.
abstract: Suppressor of cytokine signaling 1 (SOCS1) is a negative regulator of Janus kinase and the signal transducer and activation of transcription (Jak-STAT) pathway. SOCS-1 is known to be silenced by aberrant promoter methylation in human hepatocellular carcinoma (HCC) during early tumorigenesis, therefore, a strategy to restore SOCS1 expression can be utilized for cancer therapy. Here, we examined the influence of adenine nucleotide translocase 2 (ANT2) suppression by short-hairpin RNA (shRNA) on SOCS1 expression and its downstream effect in HCC. ANT2 shRNA treatment led to restoration of SOCS1 expression along with its promoter demethylation in Hep3B cells, which was accompanied by decreased DNA methyltransferase 1 (DNMT1) activity through the suppression of Ras/PI3K/Akt signaling. Restoration of SOCS1 by ANT2 knockdown, subsequently, inhibited STAT3 activity and downregulated the expression of miR-21, which has been reported to be an important onco-miR in HCC. Downregulation of miR-21 efficiently suppressed Hep3B cell proliferation in vitro with a comparable level to ANT2 shRNA treatment. ANT2 suppression by shRNA may be able to exert anticancer effects in HCC further by restoring SOCS1 expression.
authors.affiliation: Tumor Immunity Medical Research Center, Cancer Research Institute,                     Seoul National University College of Medicine, Seoul 110-799, Republic                     of Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Jang
authors.forename: Yoon-Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Choong-Eun
authors.initials: CE
authors.lastname: Lee
authors.forename: Chul-Woo
authors.initials: CW
authors.lastname: Kim
mesh_terms: D033742:Adenine Nucleotide Translocator 2 / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053613:Janus Kinase 1 / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics; D034741:RNA, Small Interfering; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D033742:Adenine Nucleotide Translocator 2; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D053613:Janus Kinase 1