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长链非编码 RNA LINC00341 通过抑制细胞迁移和凋亡来抑制结直肠癌。

The long noncoding RNA LINC00341 suppresses colorectal carcinoma by preventing cell migration and apoptosis.

机构信息

Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, China.

出版信息

Cell Biochem Funct. 2020 Apr;38(3):266-274. doi: 10.1002/cbf.3473. Epub 2020 Feb 17.

Abstract

Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies.

摘要

长链非编码 RNA(lncRNA)是普遍存在的转录本,在转录、RNA 加工和翻译水平上对基因表达起着关键作用。lncRNA 的异常表达和突变是肿瘤发生和发展的驱动力。然而,大多数 lncRNA 仍未被发现,其功能相关性的确凿实验证据仍然缺乏大多数恶性肿瘤。我们发现,长链非编码 RNA 长基因间非蛋白编码 RNA341(LINC00341)通过非转移性和转移性结直肠癌(CRC)标本的基于微阵列的筛选被异常下调;LINC00341 是一种具有未知功能的新型长基因间非蛋白编码 RNA。LINC00341 的过表达限制了肿瘤的生长并促进其凋亡。相反,LINC00341 的沉默加速了 CRC 细胞的增殖和迁移。RNA 下拉实验鉴定出 LINC00341 与 HMGB2 物理结合,并稳定 HMGB2 在细胞质中的定位。值得注意的是,LINC00341 的敲低导致 HMGB2 转移到核内,从而触发上皮间质转化(EMT)编程。此外,LINC00341 还可以促进细胞凋亡。研究意义:lncRNA 是普遍存在的转录本,在转录、RNA 加工和翻译水平上对基因表达起着关键作用。lncRNA 的异常表达和突变是肿瘤发生和发展的驱动力。然而,lncRNA 的功能仍需要进一步探索。我们的研究揭示了一个新的非编码 RNA 介导的调控网络,该网络极有可能通过防止迁移和凋亡来保护结直肠癌。研究结果将有助于进一步探索结直肠癌进展的分子细节,并激发开发有效治疗方法的努力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c701/7318321/fd2dce11ecc0/CBF-38-266-g001.jpg

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