microRNA‐665 is down‐regulated in gastric cancer and inhibits proliferation, invasion, and EMT by targeting PPP2R2A

Abstract

Recently, microRNA-665 (miR-665) has been reported to function as both tumour suppressor and oncogene in several cancer types, including gastric cancer, hepatocellular cancer, and lung cancer. However, the biological function of miR-665 and its precise mechanisms in gastric cancer (GC) have not been well clarified. The aim of this study was to study the roles of miR-665/PPP2R2A axis in GC. The levels of PPP2R2A and miR-665 were detected by quantitative PCR assay in GC tissues and cell lines. Moreover, the biological roles of miR-665 and PPP2R2A in GC cells were assessed by cell proliferation, invasion, and epithelial-mesenchymal transition (EMT).The mRNA and protein levels of PPP2R2A were determined by using quantitative PCR and Western blotting assays. Luciferase assays were used to confirm that PPP2R2A was one target of miR-665. In this study, the miR-665 level was dramatically reduced in GC tissues and cell lines, and the PPP2R2A expression was significantly enhanced. What is more, the PPP2R2A expression was negatively related to the miR-665 level in GC tissues. Furthermore, up-regulation of miR-665 obviously restrained GC cells proliferation, invasion, and EMT. We confirmed that miR-665 could directly target PPP2R2A by luciferase reporter assay. Besides, knockdown of PPP2R2A also could markedly inhibit the proliferation, invasion and EMT of GC cells.Finally, overexpression of miR-665 in GC cells partially reversed the promoted effects of PPP2R2A up-regulation. Overexpression of miR-665 restrained GC cells proliferation, invasion and EMT via regulation of PPP2R2A.Significance of the study miR-665 has been reported to function as oncogene or tumour suppressor in different cancers. However, the precise roles of miR-665 in GC have not been elucidated. Our study for the first time demonstrated that miR-665 level was significantly down-regulated in GC. Additionally, miR-665 overexpression inhibited cell growth, invasion, and EMT of GC. Moreover, our data suggested a significant negative correlation between miR-665 and PPP2R2A expression in GC. MiR-665 suppressed GC cell proliferation, invasion, and EMT by directly targeting PPP2R2A, which suggested important roles for miR-665/PPP2R2A axis in the GC pathogenesis and its potential application in cancer therapy.

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma

“…Previous studies revealed that knockdown of PR55α hindered non-small cell lung cancer cellular growth by increasing JUN T239 phosphorylation 19 . In gastric cancer, PPP2R2A expression is remarkably increased and downregulation of PPP2R2A also inhibits the proliferation and EMT of gastric cancer cells 20 . However, more studies have provided supporting towards the tumor suppressing role of PR55α.…”

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma

“…For example, MiR-222 can suppress PPP2R2A expression and promote the proliferation or invasion of papillary thyroid cancer 20 , diffuse large B-cell lymphoma 19 and HCC 17 . But, miR-665 was reported to promote PPP2R2A overexpression and inhibit the proliferation and epithelial-mesenchymal transition of gastric cancer cells 22 . Speci cally, PR55α was lowly expressed in lung cancer, thyroid gland cancer, breast cancer, diffuse large B-cell lymphoma and HCC, but highly expressed in pancreatic cancer and gastric cancer.…”

<p>Hepsin Promotes Epithelial–Mesenchymal Transition and Cell Invasion Through the miR-222/PPP2R2A/AKT Axis in Prostate Cancer</p>

“…PPP2R2A is a target gene of miR-222 and is considered to be a tumor suppressor. 24,45 Studies have indicated that PPP2R2A regulates cancer development via AKT pathways. Zhang et al reported that Pits2 promotes PPP2R2A-mediated AKT inhibition and represses pancreatic carcinogenesis.…”

“…22,23 PPP2R2A is considered a tumor suppressor and participates in the proliferation, invasion and EMT of cancer cells. [24][25][26] Additionally, PPP2R2A is reported to modulate aggressive behaviors of cancer cells by blocking the AKT signaling. 27 The AKT signaling is closely associated with EMT.…”