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Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-07-09 , DOI: 10.1038/s41419-020-02740-2
Hao Fan 1 , Yugang Ge 1 , Xiang Ma 1 , Zengliang Li 1 , Liang Shi 1 , Linling Lin 1 , Jian Xiao 1 , Wangwang Chen 1 , Peidong Ni 1 , Li Yang 1, 2 , Zekuan Xu 1
Affiliation  

Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.



中文翻译:

长的非编码RNA CCDC144NL-AS1使miR-143-3p发挥作用,并通过在胃癌中作为竞争性内源RNA来调节MAP3K7。

胃癌(GC)一直是世界范围内导致癌症死亡的最主要原因之一。已经发现长的非编码RNA(lncRNA)与多种癌症(包括GC)的致癌性和发展有关。但是,仍有许多与GC相关的lncRNA的功能性作用和分子机制尚未得到明确研究。在本文中,我们报告了尚未在GC中进行探索的lncRNA CCDC144NL-AS1,并且在GC组织中其表达明显上调,这可能是不良预后的独立预测因子。我们发现CCDC144NL-AS1表达与更大的肿瘤大小和更明显的淋巴结转移显着正相关。通过一系列的体内和体外功能实验,我们观察到CCDC144NL-AS1可以促进细胞增殖,侵袭和迁移并抑制GC中的细胞凋亡。进一步的机制研究表明,CCDC144NL-AS1充当竞争性内源RNA(ceRNA),使miR-143-3p海绵化,并上调了其直接内源靶MAP3K7在GC中的表达。综上所述,我们的结果阐明了CCDC144NL-AS1 / miR-143-3p / MAP3K7轴在GC进展中的致癌作用,为进一步了解GC机理提供了启发,并使CCDC144NL-AS1成为潜在的新型诊断和治疗靶标。 GC。

更新日期:2020-07-09
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