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

Junqi Liu, Ming Deng, Nannan Xue, Tingxuan Li, Yuexin Guo, Liang Gao, Di Zhao, Ruitai Fan

2020Molecular Therapy — Nucleic Acids61 citationsDOIOpen Access PDF

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.

Topics & Concepts

Long non-coding RNADownregulation and upregulationCancer researchCarcinogenesisBiologyCellCell growthCancerGeneGeneticsCancer-related molecular mechanisms researchKruppel-like factors researchCircular RNAs in diseases