Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of General Surgery, Liyang People's Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, Jiangsu Province, China.
Cell Death Dis. 2020 Jul 9;11(7):521. doi: 10.1038/s41419-020-02740-2.
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.
胃癌（GC）一直是全球癌症死亡的主要原因之一。长链非编码 RNA（lncRNA）已被发现与多种癌症的发生和发展有关，包括 GC。然而，仍然有许多与 GC 相关的 lncRNA 的功能作用和分子机制尚未得到明确研究。在此，我们报告了 lncRNA CCDC144NL-AS1，它在 GC 中尚未被探索，并且在 GC 组织中明显上调，可能作为预后不良的独立预测因子。我们发现 CCDC144NL-AS1 的表达与肿瘤体积较大和淋巴结转移更为明显显著正相关。通过一系列体内和体外功能实验，我们观察到 CCDC144NL-AS1 可以促进 GC 细胞的增殖、侵袭和迁移，并抑制细胞凋亡。进一步的机制研究表明，CCDC144NL-AS1 作为竞争性内源性 RNA（ceRNA），可以海绵吸附 miR-143-3p，并上调其在 GC 中的直接内源性靶标 MAP3K7 的表达。综上所述，我们的研究结果阐明了 CCDC144NL-AS1/miR-143-3p/MAP3K7 轴在 GC 进展中的致癌作用，为进一步了解 GC 的机制提供了启示，并使 CCDC144NL-AS1 成为 GC 的潜在新型诊断和治疗靶点。
