The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in gastric cancer.
The long noncoding RNA, TINCR, functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in gastric cancer.
复制标题
长的非编码RNA TINCR充当竞争性内源性RNA，可通过在胃癌中启动miR-375来调节PDK1表达。
DOI：
10.2147/ott.s137726
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发表时间：
2017
影响因子：
4
通讯作者：
Hu J
中科院分区：
文献类型：
--
作者：
Chen Z;Liu H;Yang H;Gao Y;Zhang G;Hu J
越来越多的证据表明，长链非编码RNA TINCR 在癌症进展和转移中发挥着关键作用。然而，TINCR 在人类胃癌 (GC) 进展中的总体生物学作用和机制仍然很大程度上未知。通过实时聚合酶链式反应 (PCR) 测量了 56 个配对肿瘤和邻近非肿瘤组织样本中的 TINCR 表达。通过生物信息学分析、荧光素酶测定获得了对竞争性内源 RNA (ceRNA) 机制的见解。通过体外和体内RNA干扰方法研究了TINCR和miR-375对GC细胞凋亡和增殖的影响。通过实时 PCR 和蛋白质印迹分析鉴定了 TINCR 和 PDK1 的相关性。我们的结果表明，肿瘤组织中 miR-375 水平降低，TINCR 水平升高。此外，TINCR 是 miR-375 的靶标，并抑制其在 GC 细胞中的表达。此外，TINCR的低表达增加了细胞凋亡并抑制GC细胞的增殖，而miR-375的下调则逆转了该功能。特别是，TINCR 可以负向调节 GC 细胞中 miR-375 的表达并增加 PDK1 的表达。最后，在 GC 细胞异种移植物的 TINCR 敲低中，miR-375 下调延缓了肿瘤生长抑制。长非编码 RNA TINCR 作为竞争性内源 RNA，通过在 GC 中海绵 miR-375 来调节 PDK1 表达。 TINCR/miR-375/PDK1 的 ceRNA 调控网络使我们能够更好地了解 GC 的发病机制，并促进长非编码 RNA (lncRNA) 指导的 GC 诊断的发展。
Accumulating evidence indicates that the long noncoding RNA, TINCR, plays a critical role in cancer progression and metastasis. However, the overall biological role and mechanisms of TINCR that were involved in human gastric cancer (GC) progression remain largely unknown. TINCR expression was measured in 56 paired tumor and adjacent nontumor tissue samples by real-time polymerase chain reaction (PCR). Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays. The effects of TINCR and miR-375 on GC cell apoptosis and proliferation were studied by RNA interference approaches in vitro and in vivo. The correlation of TINCR and PDK1 was identified by real-time PCR and Western blot analysis. Our results showed that miR-375 level decreased and TINCR level increased in tumor tissues. In addition, TINCR was a target of miR-375 and inhibited its expression in GC cells. Furthermore, the low expression of TINCR increased cell apoptosis and inhibited the proliferation of GC cells, while the downregulation of miR-375 reversed the function. In particular, TINCR could negatively regulate the miR-375 expression and increased the PDK1 expression in GC cells. Finally, tumor growth suppression was retarded with miR-375 downregulated in TINCR knockdown of GC cell xenografts. The long noncoding RNA TINCR functions as a competing endogenous RNA to regulate PDK1 expression by sponging miR-375 in GC. The ceRNA regulatory network of TINCR/miR-375/PDK1 allows us to better understand the pathogenesis of GC and facilitate the development of long noncoding RNA (lncRNA)-directed diagnostics in GC.