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长链非编码RNA UC001kfo通过靶向α-平滑肌肌动蛋白促进肝细胞癌的增殖和转移。

Long non-coding RNA UC001kfo promotes hepatocellular carcinoma proliferation and metastasis by targeting α-SMA.

作者信息

Pan Yanfeng, Qin Tao, Yin Shenglu, Zhang Xianqiang, Gao Xiaojuan, Mu Lifen

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China.

Department of Hepatobiliary Pancreatic Surgery, The People's Hospital of Henan Province, Zhengzhou 450000, Henan Province, China.

出版信息

Biomed Pharmacother. 2017 Mar;87:669-677. doi: 10.1016/j.biopha.2017.01.018. Epub 2017 Jan 12.

Abstract

Several long non-coding RNAs (lncRNAs) have been investigated and found to be correlated with the behaviours and prognosis of hepatocellular carcinoma (HCC); Specifically, we revealed that the lncRNA UC001kfo was differentially expressed in HCC tissues compared with normal liver tissues using lncRNA microarrays, but its functional role in cancers, including HCC, has not yet been elucidated. The present study found that the expression of UC001kfo was upregulated in HCC tissues and cell lines in comparison with tumour-adjacent tissues and normal hepatocytes, respectively. In addition, a high UC001kfo level was determined to be correlated with macro-vascular invasion and TNM stage of HCC. Specifically, patients with high UC001kfo expression displayed a significantly lower overall survival rate and progression-free survival rate. Moreover, both univariate and multivariate COX regression analyses identified TNM stage and high UC001kfo expression as risk factors for poor prognosis in HCC patients. In addition, UC001kfo was verified to promote the proliferation, metastasis and epithelial-mesenchymal transition (EMT) in HCC cells in both in vitro and in vivo assays. Mechanistically, α-SMA was indicated as a potential target gene of UC001kfo in mediating HCC metastasis. In conclusion, UC001kfo promotes HCC proliferation and metastasis by targeting α-SMA, and UC001kfo may potentially serve as a prognostic marker and a therapeutic target for treatment of HCC.

摘要

多项研究对几种长链非编码RNA(lncRNA)进行了调查,发现它们与肝细胞癌(HCC)的行为和预后相关;具体而言,我们通过lncRNA微阵列发现,与正常肝组织相比,lncRNA UC001kfo在HCC组织中差异表达,但其在包括HCC在内的癌症中的功能作用尚未阐明。本研究发现,与癌旁组织和正常肝细胞相比,UC001kfo在HCC组织和细胞系中的表达上调。此外,高水平的UC001kfo被确定与HCC的大血管侵犯和TNM分期相关。具体而言,UC001kfo高表达的患者总生存率和无进展生存率显著降低。此外,单因素和多因素COX回归分析均确定TNM分期和UC001kfo高表达是HCC患者预后不良的危险因素。此外,体外和体内实验均证实UC001kfo可促进HCC细胞的增殖、转移和上皮-间质转化(EMT)。机制上,α-SMA被认为是UC001kfo介导HCC转移的潜在靶基因。总之,UC001kfo通过靶向α-SMA促进HCC的增殖和转移,UC001kfo可能作为HCC治疗的预后标志物和治疗靶点。

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