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长链非编码 RNA 通过直接结合 RNA 抑制结直肠癌干细胞。

Long non-coding RNA inhibits the stemenss of colorectal cancer cells through directly binding to RNA.

机构信息

Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Siming District, Xiamen City, Fujian Province, China.

Department of General Surgery, The First Affiliated Hospital of Xiamen University, Siming District, Xiamen City, Fujian Province, China.

出版信息

Bioengineered. 2021 Dec;12(1):8698-8708. doi: 10.1080/21655979.2021.1977054.

Abstract

Cancer stem cells (CSCs) contribute to malignant features. Long non-coding RNA (LncRNA) has been shown to regulate tumor proliferation, migration, and invasion. However, the effects of on the CSC-like traits of colorectal cancer cells remain to be elucidated. Here, we identified that lncRNA level was remarkably lower in spheres formed by colorectal cancer cells compared to that in parental cancer cells. Further functional experiments showed that overexpression attenuated the CSC-like traits of colorectal cancer spheres, while knockdown conferred the CSC-like traits for colorectal cancer cells, as characterized by the alteration of ALDH activity, sphere-formation ability, and expression of stemness markers (). RNA-RNA interaction analysis combined with mRNA stability assay revealed that lncRNA directly interacted with mRNA 3'UTR, reduced its mRNA stability and thus inhibited expression. In addition, lncRNA -mediated effects on the CSC-like traits of colorectal cancer cells depended on expression. This work suggests that lncRNA can block the CSC-like traits in colorectal cancer cells through directly interacting with mRNA 3'UTR.

摘要

癌症干细胞(CSCs)有助于恶性特征的形成。长链非编码 RNA(LncRNA)已被证明可调节肿瘤的增殖、迁移和侵袭。然而,lncRNA 对结直肠癌细胞的 CSC 样特征的影响仍有待阐明。在这里,我们发现与亲本癌细胞相比,结直肠癌细胞形成的球体中 lncRNA 的水平显著降低。进一步的功能实验表明,lncRNA 的过表达减弱了结直肠癌细胞球体的 CSC 样特征,而 lncRNA 的敲低赋予了结直肠癌细胞的 CSC 样特征,其特征为 ALDH 活性、球体形成能力和干性标志物的表达的改变()。RNA-RNA 相互作用分析结合 mRNA 稳定性测定表明,lncRNA 直接与 mRNA 3'UTR 相互作用,降低其 mRNA 稳定性,从而抑制 表达。此外,lncRNA 对结直肠癌细胞的 CSC 样特征的影响取决于 表达。这项工作表明,lncRNA 可以通过与 mRNA 3'UTR 直接相互作用来阻断结直肠癌细胞的 CSC 样特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3ed/8806690/c04ae3188fd4/KBIE_A_1977054_F0001_OC.jpg

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