Τίτλος:
A functional microRNA library screen reveals miR-410 as a novel
anti-apoptotic regulator of cholangiocarcinoma
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Palumbo, Tiziana
Poultsides, George A.
Kouraklis, Grigorios and
Liakakos, Theodore
Drakaki, Alexandra
Peros, George and
Hatziapostolou, Maria
Iliopoulos, Dimitrios
Λέξεις-κλειδιά:
Cholangiocarcinoma; microRNA screen; miR-410; XIAP; apoptosis; microRNA
therapy
DOI:
10.1186/s12885-016-2384-0
