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

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

doi:10.1016/j.omtn.2020.01.020

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

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

Authors

Jun-Qi Liu¹, Ming Deng², Nan-Nan Xue¹, Ting-Xuan Li¹, Yue-Xin Guo¹, Liang Gao³, Di Zhao⁴, Rui-Tai Fan⁵

Affiliations

¹ Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, P.R. China.
² Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, P.R. China.
³ Center of Experimental Orthopaedics, Saarland University, Kirrberger Strasse, Building 37, 66421 Homburg, Germany.
⁴ Department of Endocrinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, P.R. China. Electronic address: zhaodi0110@126.com.
⁵ Department of Radiotherapy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, P.R. China. Electronic address: fanruitai@126.com.

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.

Keywords: Krüppel-like factor 3; apoptosis; biological characteristics; competing endogenous RNA; esophageal squamous cell carcinoma stem cells; long non-coding RNA Krüppel-like factor 3 antisense RNA 1; miR-185-5p; migration; nude mice.