Shen Sining, Li Ke, Liu Ying, Liu Xianben, Liu Baoxing, Ba Yufeng, Xing Wenqun
Department of Thoracic Surgery, Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou 450008, P.R. China.
Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University (Henan Cancer Hospital), Zhengzhou 450008, P.R. China.
Mol Ther Nucleic Acids. 2020 Jun 5;20:331-344. doi: 10.1016/j.omtn.2019.12.036. Epub 2020 Jan 15.
The interaction of long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs has been implicated in various types of cancers, including esophageal cancer (EC). The current study aimed to investigate the role of AGAP2-AS1/miR-195-5p/Fos-like antigen-1 (FOSL1) in EC progression. The expression of AGAP2-AS1, miR-195-5p, and FOSL1 in tumor tissues isolated from EC patients and EC cell lines was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the results of which illustrated that AGAP2-AS1 and FOSL1 were increased while miR-195-5p was reduced in EC. Next, the ectopic expression, knockdown, and reporter assay experiments were all employed to elucidate the mechanism of AGAP2-AS1/miR-195-5p/FOSL1 in the processes of EC cell proliferation, cell cycle, apoptosis, invasion, and migration as well as tumor growth. Knockdown of AGAP2-AS1 or overexpression of miR-195-5p reduced EC cell proliferation, migration, and invasion, blocked cell cycle entry, and elevated apoptosis. FOSL1 was found to be specifically targeted by miR-195-5p. AGAP2-AS1 was observed to upregulate FOSL1 by binding to miR-195-5p. Silencing of AGAP2-AS1 was observed to restrain the development of EC both in vitro and in vivo through upregulating miR-195-5p and downregulating FOSL1. Taken together, AGAP2-AS1 knockdown exercises suppressive effects on the development of EC through miR-195-5p-dependent downregulation of FOSL1. Therefore, targeting AGAP2-AS1 could be a future direction to develop a novel molecule-targeted therapeutic strategy for EC.
长链非编码RNA（lncRNAs）、微小RNA（miRNAs）和信使RNA（mRNAs）之间的相互作用与包括食管癌（EC）在内的多种癌症有关。本研究旨在探讨AGAP2-AS1/miR-195-5p/类Fos抗原1（FOSL1）在食管癌进展中的作用。通过定量逆转录聚合酶链反应（qRT-PCR）测定从食管癌患者和食管癌细胞系中分离的肿瘤组织中AGAP2-AS1、miR-195-5p和FOSL1的表达，结果表明，食管癌中AGAP2-AS1和FOSL1表达增加，而miR-195-5p表达降低。接下来，采用异位表达、敲低和报告基因检测实验来阐明AGAP2-AS1/miR-195-5p/FOSL1在食管癌细胞增殖、细胞周期、凋亡、侵袭和迁移以及肿瘤生长过程中的作用机制。敲低AGAP2-AS1或过表达miR-195-5p可降低食管癌细胞的增殖、迁移和侵袭能力，阻断细胞周期进程，并增加细胞凋亡。发现FOSL1是miR-195-5p的特异性靶点。观察到AGAP2-AS1通过与miR-195-5p结合上调FOSL1。观察到沉默AGAP2-AS1可通过上调miR-195-5p和下调FOSL1在体外和体内抑制食管癌的发展。综上所述，敲低AGAP2-AS1通过miR-195-5p依赖性下调FOSL1对食管癌的发展发挥抑制作用。因此，靶向AGAP2-AS1可能是未来开发食管癌新型分子靶向治疗策略的一个方向。
