Long non-coding RNA UCA1 indicates an unfavorable prognosis and promotes tumorigenesis via regulating AKT/GSK-3β signaling pathway in cholangiocarcinoma
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Yi Xu1,2, Yue Yao2, Kaiming Leng1, Zhenglong Li1,2, Wei Qin1,2, Xiangyu Zhong1, Pengcheng Kang1, Ming Wan1, Xingming Jiang1 and Yunfu Cui1
1Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China
2The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Heilongjiang, China
Yunfu Cui, email: firstname.lastname@example.org
Xingming Jiang, email: email@example.com
Keywords: cholangiocarcinoma; lncRNA; UCA1; EMT; AKT
Received: July 18, 2017 Accepted: September 21, 2017 Published: October 16, 2017
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 in vitro and in vivo. 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 (P = 0.007), lymph node invasion (P = 0.027), TNM stage (P = 0.004) and postoperative recurrence (P = 0.033) of CCA patients. Besides, UCA1 could function as an independent prognostic predictor for overall survival in patients with CCA (P = 0.014). For the part of functional assays, knockdown of UCA1 could attenuate CCA cell growth both in vitro and in vivo. 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.
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