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长链非编码 RNA VIM-AS1 通过诱导 EMT 促进结直肠癌的进展和转移。

Long noncoding RNA VIM-AS1 promotes colorectal cancer progression and metastasis by inducing EMT.

机构信息

Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.

Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.

出版信息

Eur J Cell Biol. 2018 May;97(4):279-288. doi: 10.1016/j.ejcb.2018.04.004. Epub 2018 Apr 7.

Abstract

Emerging evidence indicates that lncRNAs play crucial roles in the initiation and progression of various malignant tumors. VIM-AS1 RNA is an lncRNA that transcribes from a shared bidirectional promoter with vimentin mRNA and its function in cancer cells is largely unknown. This study assessed the clinical significance of VIM-AS1 expression in colorectal cancer (CRC). We found that the VIM-AS1 transcript was significantly upregulated in high-grade, lymph node metastasis and vascular invasion tumors. Loss-of-function experiments revealed that the downregulation of VIM-AS1 could inhibit tumor cell proliferation by inducing apoptosis, cellular senescence and arresting the cell cycle. Moreover, the obtained data demonstrated that VIM-AS1 might play a crucial role in cell migration as well as the epithelial to mesenchymal transition (EMT) of CRC cells. Collectively, for the first time, our data provide novel evidence for the biological and clinical significance of VIM-AS1 expression in CRC. Further, the findings of this study suggest that VIM-AS1 promotes tumor growth and metastasis by inducing EMT in CRC cells and could be considered as a novel tumor marker with probable value in diagnosis and CRC treatment.

摘要

越来越多的证据表明,长链非编码 RNA(lncRNA)在各种恶性肿瘤的发生和发展中起着至关重要的作用。VIM-AS1 RNA 是一种从波形蛋白 mRNA 的共享双向启动子转录而来的 lncRNA,其在癌细胞中的功能尚不清楚。本研究评估了 VIM-AS1 在结直肠癌(CRC)中的表达的临床意义。我们发现,在高级别、淋巴结转移和血管侵犯的肿瘤中,VIM-AS1 转录本显著上调。功能丧失实验表明,下调 VIM-AS1 可通过诱导细胞凋亡、细胞衰老和阻止细胞周期来抑制肿瘤细胞增殖。此外,获得的数据表明,VIM-AS1 可能在 CRC 细胞的迁移以及上皮间质转化(EMT)中发挥重要作用。总之,我们的数据首次为 VIM-AS1 在 CRC 中的表达提供了新的生物学和临床意义的证据。此外,本研究的结果表明,VIM-AS1 通过诱导 EMT 促进 CRC 细胞的肿瘤生长和转移,并且可以被认为是一种新型的肿瘤标志物,可能在 CRC 的诊断和治疗中具有潜在的价值。

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