Xu Yi, Wang Zhidong, Jiang Xingming, Cui Yunfu
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, 150086, China.
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China.
Biomed Pharmacother. 2017 Aug;92:17-23. doi: 10.1016/j.biopha.2017.05.061. Epub 2017 May 18.
Cholangiocarcinoma (CCA) is a deadly disease that poorly responds to chemotherapy and radiotherapy and whose incidence has increased worldwide. Furthermore, long noncoding RNAs (lncRNAs) play important roles in multiple biological processes, including tumorigenesis. Specifically, H19, the first discovered lncRNA, has been reported to be overexpressed in diverse human carcinomas, but the overall biological role and clinical significance of H19 in CCA remains unknown. In the present study, expression levels of H19 were investigated in CCA tissues and cell lines and were correlated with clinicopathological features. Moreover, we explored the functional roles of H19 depletion in QBC939 and RBE cells, including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results indicated that H19 was upregulated in CCA tissue samples and cell lines, and this upregulation was associated with tumor size, TNM stage, postoperative recurrence and overall survival in 56 patients with CCA. Moreover, knockdown of H19 followed by RNA silencing restrained cell proliferation and promoted apoptosis. In addition, H19 suppression impaired migration and invasion potential by reversing EMT. Overall, our findings may help to develop diagnostic biomarkers and therapeutics that target H19 for the treatment of CCA.
胆管癌(CCA)是一种对化疗和放疗反应不佳的致命疾病,其发病率在全球范围内呈上升趋势。此外,长链非编码RNA(lncRNA)在包括肿瘤发生在内的多个生物学过程中发挥着重要作用。具体而言,首个被发现的lncRNA H19已被报道在多种人类癌症中过表达,但H19在CCA中的整体生物学作用和临床意义仍不清楚。在本研究中,我们调查了H19在CCA组织和细胞系中的表达水平,并将其与临床病理特征相关联。此外,我们探讨了H19缺失在QBC939和RBE细胞中的功能作用,包括细胞增殖、凋亡、迁移、侵袭和上皮-间质转化(EMT)。结果表明,H19在CCA组织样本和细胞系中上调,这种上调与56例CCA患者的肿瘤大小、TNM分期、术后复发和总生存期相关。此外,通过RNA沉默敲低H19可抑制细胞增殖并促进凋亡。此外,H19抑制通过逆转EMT损害迁移和侵袭潜能。总体而言,我们的研究结果可能有助于开发针对H19的诊断生物标志物和治疗方法来治疗CCA。