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长非编码 RNA LINC01133 通过与 SRSF6 相互作用抑制结直肠癌细胞的上皮-间充质转化和转移。

Long non-coding RNA LINC01133 inhibits epithelial-mesenchymal transition and metastasis in colorectal cancer by interacting with SRSF6.

机构信息

Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Zhejiang, China.

Department of Pathology, Key Laboratory of Disease Proteomics of Zhejiang Province, School of Medicine, Zhejiang University, Zhejiang, China.

出版信息

Cancer Lett. 2016 Oct 1;380(2):476-484. doi: 10.1016/j.canlet.2016.07.015. Epub 2016 Jul 18.

Abstract

Long non-coding RNAs (lncRNAs) play crucial roles in many biological and pathological processes, including tumor metastasis. Here we reported a novel lncRNA, LINC01133 that was downregulated by TGF-β, which could inhibit epithelial-mesenchymal transition (EMT) and metastasis in colorectal cancer (CRC) cells. An alternative splicing factor SRSF6 was identified to directly interact with LINC01133, and SRSF6 promoted EMT and metastasis in CRC cells independent of LINC01133 And we confirmed that the EMT process was regulated by LINC01133 in CRC cells dependent on the presence of SRSF6. The observation for LINC01133 to inhibit metastasis was also verified in vivo. Moreover clinical data showed that the LINC01133 expression was positively correlated with E-cadherin, and negatively correlated with Vimentin, and there was a robust association of low LIINC01133 expression in tumors with poor survival in CRC samples. These data suggest that LINC01133 inhibits the EMT and metastasis by directly binding to SRSF6 as a target mimic, and may serve as a prognostic biomarker and an effective target for anti-metastasis therapies for CRC.

摘要

长链非编码 RNA(lncRNA)在许多生物和病理过程中发挥着关键作用,包括肿瘤转移。在这里,我们报道了一种新型的 lncRNA,LINC01133,它被 TGF-β下调,可抑制结直肠癌(CRC)细胞中的上皮-间充质转化(EMT)和转移。鉴定出一种剪接因子 SRSF6 可直接与 LINC01133 相互作用,并且 SRSF6 独立于 LINC01133 促进 CRC 细胞中的 EMT 和转移。我们证实,CRC 细胞中的 EMT 过程受 LINC01133 调节,这依赖于 SRSF6 的存在。LINC01133 抑制转移的观察结果在体内也得到了验证。此外,临床数据表明,LINC01133 的表达与 E-钙粘蛋白呈正相关,与波形蛋白呈负相关,并且在 CRC 样本中,肿瘤中 LINC01133 表达水平低与生存不良之间存在显著关联。这些数据表明,LINC01133 通过直接作为靶标模拟物与 SRSF6 结合来抑制 EMT 和转移,并且可能作为 CRC 患者的预后生物标志物和有效的抗转移治疗靶标。

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