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长链非编码RNA KLF3-AS1通过削弱miR-185-5p靶向的KLF3抑制作用来抑制食管鳞状细胞癌的细胞迁移和侵袭。

lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition.

作者信息

Liu Jun-Qi, Deng Ming, Xue Nan-Nan, Li Ting-Xuan, Guo Yue-Xin, Gao Liang, Zhao Di, Fan Rui-Tai

机构信息

Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, P.R. China.

Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.

出版信息

Mol Ther Nucleic Acids. 2020 Jun 5;20:231-241. doi: 10.1016/j.omtn.2020.01.020. Epub 2020 Jan 25.

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common cancer occurring in males and females worldwide. Accumulating evidence continues to highlight the crucial roles of long non-coding RNAs (lncRNAs) in the process of tumorigenesis. However, the regulatory mechanism of lncRNAs in ESCC remains unclear. The aim of this study is to elucidate the role of lncRNA Krüppel-like factor 3 antisense RNA 1 (KLF3-AS1) in ESCC by regulating miR-185-5p and KLF3. Initially, ESCC cell spheres with stem cell-like properties were prepared by suspension culture, and subsequently characterized by assessing colony formation ability and stem cell markers. LncRNA KLF3-AS1 was found to be poorly expressed in ESCC and could upregulate the expression of KLF3 by binding to miR-185-5p. lncRNA KLF3-AS1 upregulation was observed to inhibit miR-185-5p, thereby contributing to decreased expression of SOX2 and Oct4 (octamer-binding transcription factor 4). Furthermore, enhancement of lncRNA KLF3-AS1 resulted in reduced colony formation ability, cell invasion and migration, and tumor volume in vivo while promoting cell apoptosis in ESCC through downregulation of miR-185-5p. Collectively, this study indicated that lncRNA KLF3-AS1 inhibited ESCC cell invasion and migration by impairing miR-185-5p-mediated inhibition of KLF3, highlighting a promising novel potential target for ESCC treatment.

摘要

食管鳞状细胞癌(ESCC)是一种在全球男性和女性中都常见的癌症。越来越多的证据不断凸显长链非编码RNA(lncRNAs)在肿瘤发生过程中的关键作用。然而,lncRNAs在ESCC中的调控机制仍不清楚。本研究的目的是通过调控miR-185-5p和Krüppel样因子3(KLF3)来阐明lncRNA KLF3反义RNA 1(KLF3-AS1)在ESCC中的作用。首先,通过悬浮培养制备具有干细胞样特性的ESCC细胞球,随后通过评估集落形成能力和干细胞标志物进行表征。发现lncRNA KLF3-AS1在ESCC中表达较低,并且可以通过与miR-185-5p结合来上调KLF3的表达。观察到lncRNA KLF3-AS1的上调抑制了miR-185-5p,从而导致性别决定区Y框蛋白2(SOX2)和八聚体结合转录因子4(Oct4)的表达降低。此外,lncRNA KLF3-AS1的增强导致体内集落形成能力、细胞侵袭和迁移以及肿瘤体积减小,同时通过下调miR-185-5p促进ESCC细胞凋亡。总的来说,本研究表明lncRNA KLF3-AS1通过削弱miR-185-5p介导对KLF3的抑制作用来抑制ESCC细胞侵袭和迁移,凸显了其作为ESCC治疗有前景的新型潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/94a7/7078507/1611f7bc8022/gr1.jpg

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