lncRNA GAS5 Inhibits Cell Migration and Invasion and Promotes Autophagy by Targeting miR-222-3p via the GAS5/PTEN-Signaling Pathway in CRC

摘要

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 was 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 small interfering (si)-lncRNA GAS5, overexpressing (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 (AVOs) were examined respectively. Xenografts in nude mice were also performed to detect tumorigenesis in vivo. Results suggested that the downregulation of lncRNA GAS5 decreased the expressions 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 and 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 a competing endogenous RNA (ceRNA) of miR-222-3p, thus inhibiting CRC cell migration and invasion and promoting cell autophagy.