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作为竞争性内源RNA的Linc00483通过激活丝裂原活化蛋白激酶调控胃癌细胞的增殖和凋亡。

Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.

作者信息

Li Defeng, Yang Meifeng, Liao Aijun, Zeng Bing, Liu Diqun, Yao Yuhong, Hu Guangsheng, Chen Xuanmin, Feng Zhiqiang, Du Yanlei, Zhou Youlian, He Jie, Nie Yuqiang

机构信息

Department of Gastroenterology and Hepatology, Guangzhou Digestive Disease Center, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, China.

Guangzhou Key Laboratory of Digestive Disease, Guangzhou First People's Hospital, Guangzhou, China.

出版信息

J Cell Mol Med. 2018 Aug;22(8):3875-3886. doi: 10.1111/jcmm.13661. Epub 2018 May 15.

Abstract

Long non-coding RNAs (lncRNAs) are important regulators of many cellular processes, and their aberrant expression and/or function is associated with many different diseases, including cancer. However, the identification of functional lncRNAs in gastric cancer is still a challenge. In this study, we describe a novel functional lncRNA, linc00483, that is upregulated and associated with tumorigenesis, tumour size, metastasis and poor prognosis in gastric cancer. In our study, linc00483 promoted gastric cancer cell proliferation, invasiveness and metastasis in vitro and in vivo. Mechanistically, upregulated expression of linc00483 in gastric cancer acts as a sponge to absorb endogenous tumour suppressor miR-30a-3p. Furthermore, it restores SPAG9 expression, which is negatively regulated by miR-30a-3p, and actives MAPK signaling pathway in gastric cancer cells. Thus, linc00483 is an oncogenic lncRNA in gastric cancer and targeting linc00483 or its pathway can potentially be useful in development of targeted therapies for patients with gastric cancer. Our results show that linc00483 is an important regulator in carcinogenesis and may be a useful biomarker to predict prognosis of gastric cancer patients. We believe our findings are novel and will be of interest to scientists working in many areas related to biomarkers in cancer.

摘要

长链非编码RNA(lncRNAs)是许多细胞过程的重要调节因子,其异常表达和/或功能与包括癌症在内的许多不同疾病相关。然而,在胃癌中鉴定功能性lncRNAs仍然是一项挑战。在本研究中,我们描述了一种新型功能性lncRNA,即linc00483,它在胃癌中上调,并与肿瘤发生、肿瘤大小、转移及不良预后相关。在我们的研究中,linc00483在体外和体内均促进胃癌细胞的增殖、侵袭和转移。机制上,胃癌中linc00483表达上调可作为海绵吸附内源性肿瘤抑制因子miR-30a-3p。此外,它可恢复受miR-30a-3p负调控的SPAG9表达,并激活胃癌细胞中的MAPK信号通路。因此,linc00483是胃癌中的一种致癌lncRNA,靶向linc00483或其信号通路可能对胃癌患者靶向治疗的开发有用。我们的结果表明,linc00483是致癌过程中的一个重要调节因子,可能是预测胃癌患者预后的有用生物标志物。我们相信我们的发现是新颖的,并且会引起许多从事癌症生物标志物相关领域研究的科学家的兴趣。

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