lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition
lncRNA KLF3-AS1 Suppresses Cell Migration and Invasion in ESCC by Impairing miR-185-5p-Targeted KLF3 Inhibition
复制标题
DOI：
10.1016/j.omtn.2020.01.020
复制
发表时间：
2020-06-05
影响因子：
8.8
通讯作者：
Fan, Rui-Tai
中科院分区：
文献类型：
--
作者：
Liu, Jun-Qi;Deng, Ming;Fan, Rui-Tai
食管鳞状细胞癌（ESCC）是一种常见的恶性肿瘤，好发于男性和女性.越来越多的证据表明长链非编码RNA（lncRNA）在肿瘤发生过程中的重要作用。然而，lncRNA在食管鳞癌中的调控机制尚不清楚。本研究的目的是阐明lncRNA Kruppel样因子3反义RNA 1（KLF 3-AS 1）通过调控miR-185- 5 p和KLF 3在食管鳞癌中的作用。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来表征。LncRNA KLF 3-AS 1在食管鳞癌中表达较低，可通过与miR-185- 5 p结合上调KLF 3的表达。观察到lncRNA KLF 3-AS 1上调抑制miR-185- 5 p，从而有助于降低SOX 2和Oct 4（八聚体结合转录因子4）的表达。此外，lncRNA KLF 3-AS 1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的降低，同时通过下调miR-185- 5 p促进ESCC中的细胞凋亡。总的来说，这项研究表明，lncRNA KLF 3-AS 1通过削弱miR-185- 5 p介导的KLF 3抑制作用来抑制ESCC细胞侵袭和迁移，突出了ESCC治疗的有希望的新的潜在靶点。
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 Kruppel-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.