Search

// Chia-Yen Dai 1, 2, 3, 4, 5, 6, * , Yi-Shan Tsai 1, * , Wen-Wen Chou 1 , Tawei Liu 1 , Chung-Feng Huang 1, 2, 4 , Shu-Chi Wang 3 , Pei-Chien Tsai 1 , Ming-Lun Yeh 1, 4, 5 , Ming-Yen Hsieh 1 , Ching-I Huang 1, 5 , Shang-Yin Vanson Liu 7 , Jee-Fu Huang 1, 4 , Wan-Long Chuang 1, 4, 6 and Ming-Lung Yu 1, 2, 3, 4, 5, 6, 8 1 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 2 Department of Occupational and Environmental Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 3 Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan 4 Faculty of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan 7 Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung, Taiwan 8 Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan * These authors contributed equally to this work Correspondence to: Ming-Lung Yu, email: fish6069@gmail.com Keywords: miR-125b; HCV; IL-6; STAT3; HCV Received: July 28, 2017 Accepted: December 01, 2017 Published: January 10, 2018 ABSTRACT Background/Aims: MicroRNA-125b (miR-125b) has been found to regulate inflammation and acts as an oncogene in many cancers. The mechanisms of miR-125b expression during hepatitis C virus (HCV) infection remain to be clarified. The present study aims to identify the factors that might regulate miR-125b expression in HCV infection. Results: High expression of miR-125b was found to correlate with HCV infection in replicon cells and in sera from HCV-infected patients, whereas the miR-125b inhibitor reduced HCV gene expression. The interleukin 6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway plays an inducible effect on miR-125b gene expression. STAT3 siRNA or inhibitor could reduce HCV replication. Materials and Methods: HCV replicon cells Con1 (type 1b) and Huh7/Ava5 (type 1b) were treated with 17-hydroxy-jolkinolide B (HJB) or STAT3 siRNA. Cell viability assay and Renilla Luciferase Assay were used. Fragments of the miR-125b-1 promoter were constructed for the luciferase reporter assay. PSMB8, PSMB9, miR-125b-1, and miR-125b-2 expression was determined using TaqMan ® Gene Expression Assays. Western blot analysis was performed to assess protein abundance. Conclusions: This study elucidates a novel pathway for miR-125b in the pathogenesis of chronic HCV infection and suggests it as a possible target for treating HCV infection.

// Elena Vendramini 1, 2, 3 , Marco Giordan 1 , Emanuela Giarin 1 , Barbara Michielotto 1 , Grazia Fazio 4 , Gianni Cazzaniga 4 , Andrea Biondi 4 , Daniela Silvestri 4 , Maria Grazia Valsecchi 5 , Martina U. Muckenthaler 6 , Andreas E. Kulozik 6 , Valter Gattei 7 , Shai Izraeli 2, 3 , Giuseppe Basso 1 and Geertruy te Kronnie 1 1 Department of Women’s and Children’s Health, University of Padova, Padova, Italy 2 Edmond and Lily Safra Children’s Hospital, Sheba Medical Center, Ramat Gan, Israel 3 Tel Aviv University, Tel Aviv, Israel 4 Centro Ricerca Tettamanti, Clinica Pediatrica, University of Milano-Bicocca, Monza, Italy 5 School of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy 6 Department of Pediatric Oncology Hematology, University of Heidelberg, Heidelberg, Germany 7 Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, I.R.C.C.S., Aviano (PN), Italy Correspondence to: Elena Vendramini, email: elena.vendramini@gmail.com Keywords: B cell precursor acute lymphoblastic leukemia, ERG aberrations, noncoding RNAs, miR-125, SNORD116 Received: June 29, 2016 Accepted: March 04, 2017 Published: March 21, 2017 ABSTRACT ERG-related leukemia is a B cell precursor acute lymphoblastic leukemia (BCP ALL) subtype characterized by aberrant expression of DUX4 and ERG transcription factors, and highly recurrent ERG intragenic deletions. ERG-related patients have remarkably favorable outcome despite a high incidence of inauspicious IKZF1 aberrations. We describe clinical and genomic features of the ERG-related cases in an unselected cohort of B-other BCP ALL pediatric patients enrolled in the AIEOP ALL 2000 therapeutic protocol. We report a small noncoding RNA signature specific of ERG-related group, with up-regulation of miR-125b-2 cluster on chromosome 21 and several snoRNAs in the Prader-Willi locus at 15q11.2, including the orphan SNORD116 cluster.