OncoTargets and Therapy (Dec 2019)
Knockdown of lncRNA HOXA-AS2 Inhibits Viability, Migration and Invasion of Osteosarcoma Cells by miR-124-3p/E2F3
Abstract
Linyi Wang,1 Lijuan Wang,2 Xinhua Zhang1 1Department of Spinal Trauma Surgery, Shouguang People’s Hospital of Shandong Province, Shandong 262700, People’s Republic of China; 2Department of Anesthesiology, Shouguang People’s Hospital of Shandong Province, Shouguang, Shandong 262700, People’s Republic of ChinaCorrespondence: Xinhua ZhangDepartment of Anesthesiology, Shouguang People’s Hospital of Shandong Province, St. 45 Health, Shouguang, Shandong 262700, People’s Republic of ChinaTel +86-0536-5261667Email [email protected]: Osteosarcoma (OS) is one of the most frequent bone malignancies. Long noncoding RNAs (lncRNAs) have been revealed to participate in many cancers, including OS. This study aimed to explore the biological function of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) and its potential mechanism in OS progression.Methods: Twenty-seven OS patients were recruited for this study. U2OS and MG-63 cells were cultured for in vitro analyses. The levels of HOXA-AS2, microRNA-124-3p (miR-124-3p) and E2F transcription factor 3 (E2F3) were measured by quantitative real-time polymerase chain reaction or Western blot. OS progression was investigated by cell viability, migration and invasion using cell counting kit-8 or trans-well assay. The interaction among HOXA-AS2, miR-124-3p and E2F3 was explored by bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation and biotinylated RNA pull-down. Xenograft model was established by injecting U2OS cells into nude mice.Results: HOXA-AS2 expression was increased in OS tissues and cells and associated with poor survival of patients. Knockdown of HOXA-AS2 inhibited cell viability, migration and invasion in OS cells. miR-124-3p could bind with HOXA-AS2 and its deficiency reversed the suppressive role of HOXA-AS2 knockdown. Moreover, E2F3 acted as a target of miR-124-3p and positively regulated by HOXA-AS2. Silence of E2F3 suppressed OS progression, which was abolished by miR-124-3p exhaustion. Interference of HOXA-AS2 attenuated U2OS xenograft tumor growth via upregulating miR-124-3p and downregulating E2F3.Conclusion: HOXA-AS2 silence impeded OS progression possibly by functioning as a decoy of miR-124-3p to target E2F3, indicating novel evidence of HOXA-AS2 as a promising therapeutic target of OS.Keywords: osteosarcoma, HOXA-AS2, miR-124-3p, E2F3
