A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

BMC Cancer

Research Article

Grigorios Kouraklis¹  Theodore Liakakos²  George Peros³  Tiziana Palumbo⁴  Dimitrios Iliopoulos⁴  Maria Hatziapostolou⁵  George A. Poultsides⁶  Alexandra Drakaki⁷ 

[1] 2nd Department of Propedeutic Surgery, University of Athens School of Medicine, Athens, Greece;3rd Department of Surgery, University of Athens School of Medicine, Attikon University Hospital, Athens, Greece;4th Department of Surgery, University of Athens School of Medicine, Attikon University Hospital, Athens, Greece;Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, 650 Charles E. Young Dr., CHS 44-133, 90095-7278, Los Angeles, CA, USA;Centre for Biological Sciences, University of Southampton, Southampton, UK;Center for Systems Biomedicine, Division of Digestive Diseases, David Geffen School of Medicine, UCLA, 650 Charles E. Young Dr., CHS 44-133, 90095-7278, Los Angeles, CA, USA;Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA;Division of Hematology/Oncology, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA;

关键词: Cholangiocarcinoma;    microRNA screen;    miR-410;    XIAP;    apoptosis;    microRNA therapy;   

DOI  :  10.1186/s12885-016-2384-0

 received in 2015-11-25, accepted in 2016-05-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundCholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo.MethodsA functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors.ResultsThe screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas.ConclusionsTaken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.

【 授权许可】

CC BY   
© The Author(s). 2016