Increased apoptotic activity in xenograft tumors (day 35) treated with miR-410 relative to miR-NC, assessed by caspase 3/7 ELISA assay (Promega). (PPTX 50.3 kb

Alexandra Drakaki (3475028)

Dimitrios Iliopoulos (239766)

George Peros (62220)

George Poultsides (3475037)

Grigorios Kouraklis (3475040)

Maria Hatziapostolou (239762)

Theodore Liakakos (3475031)

Tiziana Palumbo (3475034)

BMC Cancer

PubMed

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 &gt;50&nbsp;% 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

Palumbo, Tiziana

Poultsides, George A

Kouraklis, Grigorios

Liakakos, Theodore

Drakaki, Alexandra

Peros, George

Hatziapostolou, Maria

Iliopoulos, Dimitrios

eScholarship - University of California

English

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

Tiziana Palumbo

George A. Poultsides

Grigorios Kouraklis

Theodore Liakakos

Alexandra Drakaki

George Peros

Maria Hatziapostolou

Dimitrios Iliopoulos

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Additional file 1: Figure S1. of A functional microRNA library screen reveals miR-410 as a novel anti-apoptotic regulator of cholangiocarcinoma

Springer - Publisher Connector

Background: Cholangiocarcinoma 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.

 

Methods: A 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.

 

Results: The 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.

 

Conclusions: Taken 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

Б1.В.ОД.15.4 Этология и зоопсихология 2018 очная

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