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长链非编码RNA UCA1提示预后不良,并通过调控胆管癌中的AKT/GSK-3β信号通路促进肿瘤发生。

Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma.

作者信息

Xu Yi, Yao Yue, Leng Kaiming, Li Zhenglong, Qin Wei, Zhong Xiangyu, Kang Pengcheng, Wan Ming, Jiang Xingming, Cui Yunfu

机构信息

Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China.

The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, China.

出版信息

Oncotarget. 2017 Oct 16;8(56):96203-96214. doi: 10.18632/oncotarget.21884. eCollection 2017 Nov 10.

Abstract

Long non-coding RNAs (lncRNAs) have been documented to play key roles in a wide range of pathophysiological processes, including cancer initiation and progression. Recently, the aberrant expression of urothelial carcinoma associated 1 (UCA1) was observed in many types of cancers. However, its clinical relevance and exact effects in cholangiocarcinoma (CCA) remains unknown. In the present study, we aimed to investigate the clinical significance of UCA1 and evaluate its prognostic value in patients with CCA. Besides, the functional roles of UCA1 were detected both and . Moreover, potential signaling pathways were explored to clarify the molecular mechanisms underlying CCA cell proliferation. The results indicated that UCA1 transcription is enhanced in both CCA tissue samples and cell lines, and this overexpression is associated with tumor stage ( = 0.007), lymph node invasion ( = 0.027), TNM stage ( = 0.004) and postoperative recurrence ( = 0.033) of CCA patients. Besides, UCA1 could function as an independent prognostic predictor for overall survival in patients with CCA ( = 0.014). For the part of functional assays, knockdown of UCA1 could attenuate CCA cell growth both and . Besides, UCA1 facilitates apoptosis via Bcl-2/caspase-3 pathway. In addition, UCA1 regulates migration and invasion potential of CCA cells by affecting EMT. Furthermore, AKT/GSK-3β axis was activated to upregulate CCND1 expression due to overexpression of UCA1 in CCA. To summary, UCA1 might be a potentially useful prognostic biomarker and therapeutic target for CCA.

摘要

长链非编码RNA(lncRNAs)已被证明在广泛的病理生理过程中发挥关键作用,包括癌症的发生和发展。最近,在多种类型的癌症中都观察到了尿路上皮癌相关1(UCA1)的异常表达。然而,其在胆管癌(CCA)中的临床相关性和确切作用仍不清楚。在本研究中,我们旨在探讨UCA1的临床意义,并评估其在CCA患者中的预后价值。此外,还检测了UCA1在[具体方面1]和[具体方面2]的功能作用。此外,还探索了潜在的信号通路,以阐明CCA细胞增殖的分子机制。结果表明,UCA1在CCA组织样本和细胞系中的转录均增强,这种过表达与CCA患者的肿瘤分期(P = 0.007)、淋巴结浸润(P = 0.027)、TNM分期(P = 0.004)和术后复发(P = 0.033)相关。此外,UCA1可作为CCA患者总生存的独立预后预测指标(P = 0.014)。在功能实验部分,敲低UCA1可在[具体方面1]和[具体方面2]减弱CCA细胞的生长。此外,UCA1通过Bcl-2/半胱天冬酶-3途径促进细胞凋亡。此外,UCA1通过影响上皮-间质转化来调节CCA细胞的迁移和侵袭能力。此外,由于CCA中UCA1的过表达,AKT/GSK-3β轴被激活,从而上调CCND1的表达。综上所述,UCA1可能是CCA潜在有用的预后生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f35/5707093/167af9d0f40d/oncotarget-08-96203-g001.jpg

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