Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.
Linc00483 as ceRNA regulates proliferation and apoptosis through activating MAPKs in gastric cancer.
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DOI：
10.1111/jcmm.13661
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发表时间：
2018-08
影响因子：
5.3
通讯作者：
Nie Y
中科院分区：
文献类型：
--
作者：
Li D;Yang M;Liao A;Zeng B;Liu D;Yao Y;Hu G;Chen X;Feng Z;Du Y;Zhou Y;He J;Nie Y
长非编码RNA(Long Non-Coding RNAs，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多种疾病有关。然而，胃癌中功能性lncRNAs的鉴定仍然是一个挑战。在这项研究中，我们描述了一个新的功能性LncRNA，linc00483，它被上调并与胃癌的肿瘤发生、肿瘤大小、转移和不良预后有关。在我们的研究中，linc00483在体内外促进了胃癌细胞的增殖、侵袭和转移。在机制上，linc00483在胃癌中的上调表达起到海绵的作用，吸收内源性抑癌基因miR-30a-3p。此外，它还可以恢复受miR-30a-3p负调控的SPAG9的表达，并激活胃癌细胞中的MAPK信号通路。因此，linc00483在胃癌中是一种致癌的lncRNA，靶向linc00483或其途径可能对胃癌患者的靶向治疗有潜在的帮助。我们的结果表明，linc00483是一种重要的肿瘤发生调节因子，可能成为预测胃癌患者预后的有用生物标记物。我们相信，我们的发现是新颖的，将会引起致力于癌症生物标记物相关领域的科学家的兴趣。
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.
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