Inhibition of miR-10a-5p suppresses cholangiocarcinoma cell growth through downregulation of Akt pathway.
Inhibition of miR-10a-5p suppresses cholangiocarcinoma cell growth through downregulation of Akt pathway.
复制标题
抑制 miR-10a-5p 通过下调 Akt 通路抑制胆管癌细胞生长
DOI：
10.2147/ott.s182225
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发表时间：
2018
影响因子：
4
通讯作者：
Yang T
中科院分区：
文献类型：
--
作者：
Gao L;Yang X;Zhang H;Yu M;Long J;Yang T
背景胆管癌（Cholangiocarcinoma，CCA）是一种预后极差的上皮细胞恶性肿瘤.许多患者在CCA晚期被诊断，未发现危险因素。可用于CCA患者管理的治疗选择有限。因此，开发有效的靶向治疗方法是治疗CCA的当务之急。miRNAs是一类非编码小分子RNA，对靶基因起负调控作用。本研究旨在探讨miR-10a-5 p在CCA中的作用及其机制。方法用miR-10a-5 p模拟物或miR-10a-5 p抑制剂转染人CCA细胞系CCLP 1和SG-231。进行qRT-PCR以检测miR-10a-5 p水平。分析增殖、集落形成和凋亡。采用荧光素酶报告基因检测miR-10a-5 p对PTEN的靶向性。对于体内肿瘤发生测定，将具有稳定敲低的miR-10a-5 p的CCLP 1细胞或对照CCLP 1细胞皮下注射到SCID小鼠的侧腹中，并监测动物的肿瘤生长。结果miR-10a-5 p在人CCA细胞系（CCLP 1和SG-231）中表达显著上调。抑制miR-10a-5 p可显著抑制CCLP 1和SG-231的增殖并诱导凋亡。PTEN是CCA细胞中miR-10a-5 p的直接靶点。结论抑制miR-10a-5 p可通过下调Akt通路抑制CCA细胞生长。这些结果表明，miR-10a-5 p可能作为治疗CCA的潜在靶点，并有助于开发有效的治疗策略。
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.