Reciprocal repression between TUSC7 and miR-23b in gastric cancer
Reciprocal repression between TUSC7 and miR-23b in gastric cancer
复制标题
胃癌中 TUSC7 和 miR-23b 之间的相互抑制
DOI：
10.1002/ijc.29516
复制
发表时间：
2015-09-01
影响因子：
6.4
通讯作者：
Du, Xiang
中科院分区：
文献类型：
--
作者：
Qi, Peng;Xu, Mi-die;Du, Xiang
最近，长非编码RNA（lncRNA）被证明在生物过程和癌症生物学中发挥重要的调节作用。然而，lncRNA 对胃癌 (GC) 的总体病理生理学贡献仍然很大程度上未知。在这项研究中，通过微阵列鉴定了GC和配对的相邻正常组织样本中差异表达的lncRNA，并使用定量实时聚合酶链反应（qRT-PCR）进行了验证。在连续的大队列中分析了一种特定的 lncRNA，肿瘤抑制候选蛋白 7 (TUSC7)，并使用 Kaplan-Meier 方法和对数秩检验进行比较来分析生存数据。结果表明，TUSC7在GC样本中下调，并且是GC患者无病生存（DFS）和疾病特异性生存（DSS）的独立预后指标。应用功能丧失和功能获得方法，我们确定 TUSC7 在体外和体内抑制肿瘤细胞生长。此外，我们通过 p53 与 TUSC7 上游区域推定的 p53 响应元件相互作用，证明 TUSC7 是 p53 的直接转录靶标。最后，我们证明了 TUSC7 和 miR-23b 之间的相互抑制；与 TUSC7 相比，miR-23b 促进细胞生长。结果表明，TUSC7 是一种 p53 调节的肿瘤抑制因子，部分通过抑制 miR-23b 发挥作用，并且 TUSC7 可能是 GC 中的关键调节中心。有什么新消息？新数据表明，长非编码 RNA 表达可以预测胃癌存活率。之前已经证明这些转录物可以起到肿瘤抑制因子的作用，在本文中，作者研究了胃癌中的 lncRNA。首先，他们鉴定出在癌细胞中与健康细胞中表达不同的lncRNA。通过进行队列分析，他们发现携带一种名为 TUSC7 的特定 lncRNA 的患者有更大的生存机会。然后他们证明 p53 调节 TUSC7 转录，而 TUSC7 抑制 miR-23b，从而刺激细胞生长。因此，TUSC7可能充当肿瘤抑制因子。
Recently, long noncoding RNAs (lncRNAs) were demonstrated to play important regulatory roles in biological processes and cancer biology. However, the overall pathophysiological contribution of lncRNAs to gastric cancer (GC) remains largely unknown. In this study, differentially expressed lncRNAs in GC and paired adjacent normal tissue samples were identified by microarray and were validated using quantitative real-time polymerase chain reaction (qRT-PCR). One particular lncRNA, tumour suppressor candidate 7 (TUSC7), was analyzed in sequential large cohorts, and the Kaplan-Meier method with the log-rank test for comparisons was used to analyse the survival data. The results indicated that TUSC7 was downregulated in GC samples and was an independent prognostic indicator of disease-free survival (DFS) and disease-specific survival (DSS) in GC patients. Applying loss-of-function and gain-of-function approaches, we determined that TUSC7 suppressed tumour cell growth in vitro and in vivo. Furthermore, we showed that TUSC7 was a direct transcriptional target of p53 via interaction of p53 with the putative p53-response element in the upstream region of TUSC7. Finally, we demonstrated reciprocal repression between TUSC7 and miR-23b; in contrast to TUSC7, miR-23b promoted cell growth. The results indicated that TUSC7 is a p53-regulated tumour suppressor that acts in part by repressing miR-23b and that TUSC7 may be a key regulatory hub in GC.What's new? Long noncoding RNA expression could predict gastric cancer survival, new data suggest. It's been shown previously that these transcripts can function as tumor suppressors, and in this paper the authors investigate lncRNAs in gastric cancer. First, they identified lncRNAs that were expressed differently in cancer cells than healthy ones. By performing a cohort analysis they showed that patients with one particular lncRNA, called TUSC7, had a greater chance of survival. They then demonstrated that p53 regulates TUSC7 transcription, and that TUSC7 represses miR-23b, which spurs cell growth. Thus, TUSC7 may act as a tumor suppressor.