Long Non-Coding RNA GAS5 Inhibits Cell Migration, Invasion and promotes Autophagy by Targeting MicroRNA-222-3p via the GAS5/PTEN Signaling Pathway in Colorectal Cancer

Abstract Colorectal cancer (CRC) is a frequently occurring lethal disorder with heterogeneous outcomes and drug responses. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) play a critical role in carcinogenesis. Hence, the aim of this study is to investigate the role of lncRNA growth arrest-specific 5 (GAS5) in CRC cells via mediation of the microRNA-222-3p (miR-222-3p)/GAS5/phosphatase and tensin homolog (PTEN) signaling pathway. HCT116 and SW480 cells were collected and treated with si-lncRNA GAS5, oe-lncRNA GAS5, miR-222-3p mimic, miR-222-3p inhibitor or si-lncRNA GAS5 + miR-222-3p mimic. The miR-222-3p level and mRNA and protein levels of GAS5, Beclin1, light chain 3B (LC3B), PTEN and Akt were detected. Besides, cell migration, invasion and apoptosis as well as acidic vesicular organelles (AVO) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that downregulation of lncRNA GAS5 decreased the expression of Beclin1, LC3B and PTEN. When treated with oe-lncRNA GAS5 or miR-222-3p inhibitor, HCT116 and SW480 cells exhibited suppressed invasion and migration abilities and increased apoptotic cells, autophagosome and AVO activities. Moreover, overexpression of GAS5 inhibited the tumorigenesis of CRC cells in vivo. Taken together, lncRNA GAS5 upregulated the expression of PTEN by functioning as ceRNA of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.