Silencing lncRNA AGAP2-AS1 Upregulates miR-195-5p to Repress Migration and Invasion of EC Cells via the Decrease of FOSL1 Expression
Sining Shen, Ke Li, Ying Liu, Xianben Liu, Baoxing Liu, Yufeng Ba, Wenqun Xing
Abstract
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. 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.