Long non-coding RNA GAS5 suppresses pancreatic cancer metastasis through modulating miR-32-5p/PTEN axis

Abstract

BackgroundLong non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) is a well-known tumor suppressor in the pathogenesis of a variety of human cancers. The precise role of GAS5 in pancreatic cancer (PC) progression is currently unknown, so the aim of this study was to explore the functional participation of GAS5 in PC metastasis.MethodsThe expression changes of GAS5, miR-32-5p and PTEN in human PC specimens and cell lines were compared by means of molecular biology methods. Transfection of the recombinant plasmid was applied to modulate the expression levels of the target genes. RIP and RNA pull-down assays were designed to investigate the interaction between GAS5 and miR-32-5p. The effect of GAS5 and miR-32-5p on PC progression was assessed with cell proliferation, migration, invasion and apoptosis in vitro.ResultsGAS5 and PTEN protein were decreased in human PC tissues and cells, but miR-32-5p was increased. GAS5 induction greatly inhibited the proliferation, migration and invasion of PC cells PANC-1 and BxPC-3 in vitro and simultaneously induced cell apoptosis. Moreover, GAS5 positively regulated the expression of PTEN through miR-32-5p. Furthermore, GAS5 suppressed the proliferation, migration and invasion of PC cells through regulating miR-32-5p/PTEN axis. Additionally, this finding was further supported by the results of in vivo experiments.ConclusionGAS5 could positively regulate PTEN-induced tumor-suppressor pathway via miR-32-5p, thereby suppressing PC metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13578-017-0192-0) contains supplementary material, which is available to authorized users.

LncRNA growth arrest‐specific transcript 5 targets miR‐21 gene and regulates bladder cancer cell proliferation and apoptosis through PTEN

“…Study of Tao has found that GAS5 could regulate cardiac fibroblast fibrosis by targeting miR‐21 to regulate PTEN/ MMP‐2 signaling pathway . In pancreatic cancer, GAS5 inhibits metastasis of pancreatic cancer cells by modulating the miR‐32‐5p/PTEN axis . Animal experiments in this study also showed that GAS5 and miR‐21 acted as antitumors by inducing expression of GAS5.…”

Non-coding RNAs in Pancreatic Ductal Adenocarcinoma

“…GAS5 is one of the few lncRNAs that are negatively correlated with tumor development in breast cancer, malignant pleural mesothelioma and hepatocellular carcinoma (56)(57)(58). GAS5 negatively regulates miR-32-5p to promote the expression of pleiotrophin (PTEN), which can block the activation of the PI3K/Akt signaling pathway, inhibiting the proliferation and survival of PDAC cells (59). Studies have found that GAS5 overexpression can significantly inhibit both the proliferation and invasion of PANC-l and BxPC-3 cells in vitro (60).…”

Long non‐coding small nucleolar RNA host genes in digestive cancers

“…Gao et al put forward that GAS5 reduced the drug resistance of cancer cells through regulating MIR‐181c‐5p and Hippo pathway . Moreover, GAS5 could downregulate MIR‐32‐5p and increase the PTEN protein level . SNHG9 was expressed at a lower level in cancer tissues and serum than in normal tissues, and there were negative correlations with cancer stage, lymph node metastasis, disease prognosis.…”