SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer
SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer
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DOI：
10.1038/onc.2015.18
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发表时间：
2015-11-05
期刊：
影响因子：
8
通讯作者：
Shu, Y-Q
中科院分区：
文献类型：
--
作者：
Xu, T-P;Liu, X-X;Shu, Y-Q
长的非编码RNA TINCR在人类鳞癌中异常表达。然而，其在胃癌中的表达和功能仍不清楚。我们报告了TINCR在人类胃癌(GC)中的强烈上调，它被发现与肿瘤的发生和癌症的进展有关。我们还发现TINCR的过表达是由核转录因子SP1诱导的。在SGC7901和BGC823细胞中，沉默TINCR的表达抑制了细胞的增殖、集落形成、致瘤性和促进细胞凋亡，而TINCR的过表达促进了细胞的生长。机制分析表明，TINCR可与STAU1(Staufen1)蛋白结合，影响KLF2基因的稳定性和表达，进而调控细胞周期蛋白依赖性激酶基因CDKN1A/P21和CDKN2B/P15的转录和表达，从而影响胃癌细胞的增殖和凋亡。总之，我们的发现表明，TINCR有助于GC的致癌潜力，并可能成为这种疾病的潜在治疗靶点。
The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.