MicroRNA-410 Suppresses Migration and Invasion by Targeting MDM2 in Gastric Cancer

Abstract

Gastric cancer is one of the most frequent malignancies in tumors in the East Asian countries. Identifying precise prognostic markers and effective therapeutic targets is important in the treatment of gastric cancer. microRNAs (miRNAs) play important roles in tumorigenesis. However, the mechanisms by which miRNAs regulate gastric cancer metastasis remain poorly understood. In this study, we found that the levels of miR-410 in gastric cancer and cell lines were much lower than that in the normal control, respectively, and the lower level of miR-410 was significantly associated with lymph-node metastasis. Transfection of miR-410 mimics could significantly inhibit the cell proliferation, migration and invasion in the HGC-27 gastric cancer cell lines. In contrast, knockdown of miR-410 had the opposite effect on the cell proliferation, migration and invasion. Moreover, we also found that MDM2 was negatively regulated by miR-410 at the post-transcriptional level, via a specific target site with the 3′UTR by luciferase reporter assay. The expression of MDM2 was inversely correlated with miR-410 expression in gastric cancer tissues, and overexpression of MDM2 in miR-410-transfected gastric cancer cells effectively rescued the inhibition of cell proliferation and invasion caused by miR-410. Thus, our findings suggested that miR-410 acted as a new tumor suppressor by targeting the MDM2 gene and inhibiting gastric cancer cells proliferation, migration and invasion. The findings of this study contributed to the current understanding of these functions of miR-410 in gastric cancer.

MiR-410 Acts as a Tumor Suppressor in Estrogen Receptor-Positive Breast Cancer Cells by Directly Targeting ERLIN2 via the ERS Pathway

“…In glioma, miR-410 suppresses the cell proliferation and invasion by targeting MET [23]. MiR-410 plays similar roles in gastric cancer by targeting MDM2, and downregulation of miR-410 is associated with lymph-node metastasis [24]. Moreover, miR-410 enhances the radiosensitivity of gastric cancer cells and suppresses cell proliferation as well as radio-induced EMT [25].…”

Dysregulation of Vascular Endothelial Growth Factor Receptor-2 by Multiple miRNAs in Endothelial Colony-Forming Cells of Coronary Artery Disease

“…Consistently, miR-410-3p and miR-497-5p have also been reported to act as tumor suppressors in several different cancers. Decreased miR-410 expression levels have been reported in pituitary gonadotroph tumors, pancreatic tumors, and gastric tumors by targeting cyclin B1 (CCNB1) [33], angiotensin II type 1 receptor (AGTR1) [34], and MDM2 proto-oncogene (MDM2) [35], respectively. Overexpression of miR-410 in these tumor cells suppressed tumor proliferation and metastasis.…”

Downregulation of miR-410 targeting the cyclin B1 gene plays a role in pituitary gonadotroph tumors

“…24 Moreover, other previous studies have evidenced a tumor suppressor activity for this miRNA. Indeed, miR-410 has been found downregulated gliomas 19 and gastric carcinomas 25 where lower miRNA-410 expression levels significantly correlated with the presence of lymph-node metastasis. Consistently, maintenance of miR-410 expression is associated with a better overall survival in advanced serous ovarian cancer.…”