MicroRNA 520d-3p inhibits gastric cancer cell proliferation, migration, and invasion by downregulating EphA2 expression

Abstract

Aberrant expression of microRNAs (miRNAs) has been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the roles of miR-520d-3p on gastric cancer (GC) cell proliferation, migration, and invasion, and confirmed that this miRNA regulates EphA2 expression. The mRNA expression levels of miR-520d-3p and EphA2 in GC tissues and cell lines were evaluated. The clinical and prognostic significance of miR-520d-3p was assessed. The biological function of miR-520d-3p in GC cells was investigated using a methylthiazolyldiphenyl-tetrazolium bromide assay, cell cycle assay, transwell invasion assay, and wound-healing assay. miR-520d-3p expression was down-regulated and inversely correlated with the expression of EphA2 in GC tissues and cell lines. Lower expression of miR-520d-3p was associated with tumor invasion (P = 0.0357), lymph nodes metastasis (P = 0.0272), a higher clinical stage (P = 0.0041), and poorer overall survival (P = 0.0105). Luciferase assays revealed that miR-520d-3p inhibited EphA2 expression by targeting the 3'-untranslated region of EphA2 mRNA. Overexpression of miR-520d-3p dramatically inhibited the proliferation, cell cycle progression, invasion, and migration of GC cells, while down-regulation substantially promoted these properties. Moreover, c-Myc, CyclinD1, and matrix metalloproteinase-9 expression levels were down-regulated in miR-520d-3p mimic-transfected cells and up-regulated in miR-520d-3p inhibitor-transfected cells. Taken together, our data showed that miR-520d-3p appears to contribute to GC progression via the regulation of EphA2 and could serve as a novel prognostic and potential therapeutic marker.

MiR-520b/e Regulates Proliferation and Migration by Simultaneously Targeting EGFR in Gastric Cancer

“…MiR-520 also has been reported in GC [34]. However, to our knowledge, the study of the relationship between miR-520b/e and EGFR pathway in GC has not been reported.…”

Oxidative stress response and Nrf2 signaling in aging

“…Bach1, a negative regulator of Nrf2/EpRE activity, has been shown to be target of miR-196b [383], miR-155 [384], let-7b miRNA, let-7c miRNA, miR98 [385], and miR-122 [386]. Another negative regulator of Nrf2, c-Myc, was also regulated by miRNA, including miR-520d-3p [387], miRNA-135b [388], miR-34b/c [389], miR-744 [390], miR-184 [391], microRNA-135a [392], miR-145 [393] [394], miR-126 [395], miR-449c [396], miR-196b [397], miR-34a [398], miR-33b [399], miR-98 [400], miR-let-7 [400] [401] and miR-185-3p [402]. The Nrf2 partner, c-Jun is also targeted by miRNA miR-125b [403] and miR-155 [404].…”

Influence of miR‐520e‐mediated MAPK signalling pathway on HBV replication and regulation of hepatocellular carcinoma cells via targeting EphA2

“…inhibited cell proliferation and blocked p38MAPK and ERK1/2 pathways, whereas inhibiting miR-520e led to completely opposite results, and si-EphA2 reversed the effect of miR-520e inhibitor. Coincidentally, miR-520d-3p, another member of miR-520 family, could target EphA2 to suppress the proliferation, invasion and migration od gastric cancer cells, as indicated by Li et al, 44 and downregulation of EphA2 has been previously shown to inhibit Ras/MAPK pathway to inhibit tumour growth. 45 The above-mentioned findings demonstrated that miR-520e may block the downstream MAPK signalling pathway by targeting EphA2, consequently interrupting the HBV replication and cell proliferation of HBx-mediated HCC.…”