Long Non-Coding RNA AGAP2-AS1/miR-628-5p/PTN Axis Modulates Proliferation, Migration, Invasion, and Apoptosis of Glioma Cells

Yang Yan,1,* Yiping Wang,1,* Yuxia Liu,2 Tao Chen,3 Yaoli Zhu,4 Huiqing Li,5 Fangen Kong1 1Department of Neurosurgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 2Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Spine Surgery, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 4Department of Critical Care Medicine, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 5Department of Neurology, The Fifth Affiliated Hospital Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Fangen Kong Email uyangleyanwlpty@163.comPurpose: Long non-coding RNAs (lncRNAs) have been reported to be involved in a variety of cancers, including glioma. However, the exact role and underlying mechanism of lncRNA AGAP2 antisense RNA 1 (AGAP2-AS1) in glioma have not yet been fully elucidated.Methods: The expression levels of AGAP2-AS1, microRNA-628-5p (miR-628-5p) and pleiotrophin (PTN) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration and invasion were detected by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, transwell assay, respectively. Western blot assay was used to detect the protein level of PTN. The interaction between miR-628-5p and AGAP2-AS1 or PTN was predicted by bioinformatics software and confirmed by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Murine xenograft model was established to confirm the role of AGAP2-AS1 in glioma progression in vivo.Results: AGAP2-AS1 expression was upregulated in glioma tissues and cells. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion, but facilitated apoptosis in glioma cells. Moreover, AGAP2-AS1 could directly bind to miR-628-5p and its overexpression reversed the anti-tumor effect of miR-628-5p restoration on the progression of glioma cells. In addition, miR-628-5p directly targeted PTN and its inhibition abolished the inhibitory effect of PTN knockdown on the progression of glioma cells. Furthermore, AGAP2-AS1 functioned as a competing endogenous RNA (ceRNA) by sponging miR-628-5p to modulate PTN expression. Besides, AGAP2-AS1 depletion reduced tumor growth by upregulating miR-628-5p and downregulating PTN.Conclusion: AGAP2-AS1 knockdown suppressed cell proliferation, migration and invasion but promoted cell apoptosis in glioma cells by regulating miR-628-5p/PTN axis, providing novel avenues for treatment of glioma.Keywords: glioma, AGAP2-AS1, miR-628-5p, PTN, cell progression