Abstract
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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2384-0) contains supplementary material, which is available to authorized users.
Highlights
Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate
Since we were interested in identifying microRNAs that have the ability to suppress cholangiocarcinoma cell growth, we focused our interest on the microRNAs that showed the highest suppressive effects
We found that miR-410 has a seed region that matches the 3′-untranslated region (UTR) of human X-linked inhibitor of apoptosis protein (XIAP) (Fig. 3a)
Summary
MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Cholangiocarcinoma (CCAs) represents a heterogeneous group of epithelial cancers highly resistant to chemotherapy. They occur in about one to two people per 100,000 and represent approximately 7 % of all gastrointestinal cancer [1]. MicroRNAs have been involved in the pathogenesis of different types of cancer; their role and function in cholangiocarcinoma (CCA) pathogenesis has not been widely explored. Previous studies revealed that microRNA-410 is deregulated in different types of cancer, including neuroblastoma, breast cancer and prostate cancer, acting as a tumor suppressor gene [10,11,12], the role of miR-410 in cholangiocarcinoma remains to be examined
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