OncoTargets and Therapy (Oct 2018)
Inhibition of miR-10a-5p suppresses cholangiocarcinoma cell growth through downregulation of Akt pathway
Abstract
Lili Gao,1,* Xiaoping Yang,2,* Hao Zhang,2 Minghua Yu,3 Jianting Long,4 Tao Yang1 1Center for Medical Research and Innovation, 2Department of General Surgery, 3Department of Medical Oncology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, People’s Republic of China; 4Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Backgrounds: Cholangiocarcinoma (CCA) is epithelial cell malignancy with very poor prognosis. A lot of patients were diagnosed at advanced stage of CCA and no risk factors were identified. There are limited treatment options available for the management of CCA patients. It is urgent to develop effective targeted therapies for the treatment of CCA. miRNAs are small noncoding RNAs that negatively regulate the target genes. In this study, we investigated the role and mechanism of miR-10a-5p in CCA. Methods: Human CCA cell lines (CCLP1 and SG-231) were transfected with miR-10a-5p mimic or miR-10a-5p inhibitor. qRT-PCR was performed to detect the miR-10a-5p level. Proliferation, colony formation, and apoptosis were analyzed. Luciferase reporter assay was used to explore the targeting of miR-10a-5p on PTEN. For in vivo tumorigenesis assay, CCLP1 cells with stable knockdown of miR-10a-5p or control CCLP1 cells were injected subcutaneously into the flank of the SCID mice and animals were monitored for tumor growth. Results: miR-10a-5p expression was significantly upregulated in human CCA cell lines (CCLP1 and SG-231). Inhibition of miR-10a-5p significantly suppressed the proliferation and induced apoptosis in CCLP1 and SG-231. PTEN is a direct target of miR-10a-5p in CCA cells.Conclusion: Inhibition of miR-10a-5p can decrease CCA cells growth by downregulation of Akt pathway. These results indicate that miR-10a-5p may serve as a potential target for the treatment of CCA and help to develop effective therapeutic strategies. Keywords: miR-10a-5p, cholangiocarcinoma, PTEN, Akt, liver, proliferation
