Long non-coding RNA UCA1 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells through targeting microRNA-122
Long non-coding RNA UCA1 promotes proliferation and invasion of intrahepatic cholangiocarcinoma cells through targeting microRNA-122
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DOI：
10.3892/etm.2019.7564
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发表时间：
2019-07-01
影响因子：
2.7
通讯作者：
Peng, Chuang
中科院分区：
文献类型：
--
作者：
Li, Ou;Yi, Weimin;Peng, Chuang
尿路上皮癌相关的长非编码RNA 1(UCA1)在包括胆管细胞癌在内的多种常见的人类恶性肿瘤中均有表达，但UCA1在肝内胆管细胞癌(ICC)中的表达和功能尚不清楚。在本研究中，UCA1在ICC组织和细胞系中的表达分别显著高于癌旁非肿瘤组织和人肝内胆管上皮细胞系。UCA1的高表达与ICC的淋巴结转移和临床T分期显著相关。此外，UCA1高表达的ICC患者的生存时间短于UCA1低表达的患者。UCA1基因敲除可显著降低ICC细胞的增殖和侵袭能力，而异位过表达UCA1可显著促进ICC细胞的增殖和侵袭。此外，还发现UCA1直接与microRNA(MiR)-122结合，负向调节其在ICC细胞中的表达。此外，miR-122模拟物阻断了UCA1对ICC细胞增殖和侵袭的促进作用。此外，在ICC组织中miR-122和UCA1的表达呈负相关。总之，本研究表明，LncRNA UCA1至少部分地通过靶向miR-122促进ICC细胞的增殖和侵袭，提示UCA1/miR-122的相互作用可能成为治疗ICC的潜在靶点。
Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) has a role in various common types of human malignancy, including cholangiocarcinoma; however, the expression and function of UCA1 in intrahepatic cholangiocarcinoma (ICC) has remained elusive. In the present study, it was observed that UCA1 expression was significantly upregulated in ICC tissues and cell lines compared with that in the adjacent non-tumour tissues and a human intrahepatic biliary epithelial cell line, respectively. The increased expression of UCA1 was significantly associated with lymph node metastasis and clinical T-stage in ICC. Furthermore, the ICC patients with high expression of UCA1 had a shorter survival time when compared with that of patients with low UCA1 expression. Knockdown of UCA1 caused a significant decrease in ICC cell proliferation and invasion, while ectopic overexpression of UCA1 significantly promoted the proliferation and invasion of ICC cells. Furthermore, it was revealed that UCA1 directly binds to microRNA (miR)-122 to negatively regulate its expression in ICC cells. In addition, miR-122 mimics abrogated the promoting effects of UCA1 on ICC cell proliferation and invasion. In addition, an inverse correlation between miR-122 and UCA1 expression in ICC tissues was observed. In conclusion, the present study demonstrates that the lncRNA UCA1 promotes ICC cell proliferation and invasion at least in part by targeting miR-122, suggesting that the UCA1/miR-122 interaction may become a potential therapeutic target for the treatment of ICC.