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lncRNA TP73-AS1 的表达增强预示着胆管癌的不良表型,并在体外和体内发挥致癌特性。

Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo.

机构信息

Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

Department of Education, Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China.

出版信息

Biomed Pharmacother. 2018 Oct;106:260-266. doi: 10.1016/j.biopha.2018.06.045. Epub 2018 Jun 28.

Abstract

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.

摘要

胆管癌(CCA)是一种具有全球发病率上升趋势的最具侵袭性恶性肿瘤之一。各种证据表明,异常表达的长非编码 RNA(lncRNA)在肿瘤发生和进展中发挥重要作用。TP73-AS1 是一种新型与癌症相关的 lncRNA,它有助于几种恶性肿瘤的发展。然而,其在 CCA 中的临床价值和潜在作用尚不清楚。使用 RT-qPCR 测量 CCA 组织和配对非肿瘤组织中 TP73-AS1 的表达水平,并分析 TP73-AS1 表达与临床病理特征之间的关联。此外,还在体外和体内检测了 TP73-AS1 在 CCA 中的功能作用。结果表明,TP73-AS1 的转录在 CCA 组织样本和细胞系中均增强,这种上调与 CCA 患者较大的肿瘤大小(p=0.008)和较晚期的 TNM 分期(p=0.026)密切相关。在功能测定部分,沉默 TP73-AS1 可减弱 CCA 细胞在体外和体内的生长。此外,沉默 TP73-AS1 通过激活 caspase-3 和 caspase-9 促进细胞凋亡。重要的是,TP73-AS1 的表达不会影响 HIBEC 细胞的生长和凋亡。此外,TP73-AS1 还可以促进 CCA 细胞的迁移和侵袭能力。总之,这些发现可能有助于为 CCA 患者开发潜在的治疗靶点。

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