Abstract
BackgroundDownregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism.MethodsMultiply biomedical databases query and KEGG pathway enrichment assay were used to infilter possible target genes and downstream pathways regulated by miR-338-3p. Overexpression miR-338-3p lentiviral vectors were transfected into ovarian cancer OVCAR-3 and OVCAR-8 cells, cell proliferation, migration and invasion were analyzed by MTT, colony formation, transwell, Matrigel assay and xenograft mouse model. One 3′-untranslated regions (UTRs) binding target gene of miR-338-3p, MACC1 (MET transcriptional regulator MACC1), and its regulated gene MET and downstream signaling pathway activities were examined by western blot.ResultsBiomedical databases query indicated that miR-338-3p could target MACC1 gene and regulate Met, downstream Wnt/Catenin beta and MEK/ERK pathways. Rescue of miR-338-3p could inhibit the proliferation, migration and invasion of ovarian cancer cells, and suppress the growth and metastasis of xenograft tumor. Restoration of miR-338-3p could attenuate MACC1 and Met overexpression induced growth, epithelial to mesenchymal transition (EMT) and activities of Wnt/Catenin beta and MEK/ERK signaling in vitro and in vivo.ConclusionsThe present data indicated that restoration of miR-338-3p could suppress the growth and metastasis of ovarian cancer cells, which might due to the inhibition of proliferation and EMT induced by MACC1, Met and its downstream Wnt/Catenin beta and MEK/ERK signaling pathways.
Highlights
Downregulation of microRNA-338-3p was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers
Results miR-338-3p was downregulated in ovarian cancer tissues and could target MET transcriptional regulator MACC1 (MACC1) The expression profiles of miR-338-3p in ovarian cancer queried in multiply biomedical databases well confirmed to our previous report [14]
Based on multiply database interactive verification, miR-338-3p could bind to the 3′- untranslated regions (UTRs) of MACC1 and MACC1 was one of downstream target genes of miR-338-3p (Fig. 1f,g, Additional file 2) which was demonstrated by several independent reports in different cancer cells using dual-luciferase reporter assay or biotin-avidin pull-down assay [24,25,26,27,28,29]
Summary
Downregulation of microRNA-338-3p (miR-338-3p) was detected in many malignant tumors, which indicated miR-338-3p might serve as a role of antioncogene in those cancers. The present study aimed to explore the roles of miR-338-3p in the growth and metastasis of ovarian cancer cells and elaborate the underlying possible molecular mechanism. Emerging evidences showed upregulation of miR-338-3p could target different downstream genes and signaling pathways to inhibit malignant cells proliferation, migration and invasion in rectal cancer, gastric cancer, lung cancer, neuroblastoma and liver cancer, which indicated miR-338-3p might be associated with the initiation and progression of these human cancers [7,8,9,10,11]. Few researches involved in the relation between miR338-3p and ovarian cancer. One study indicated miR-3383p could inhibit the proliferation and metabolism of ovarian cancer, and the other showed miR-338-3p could suppress growth of ovarian epithelial carcinoma cells by targeting Runx2 [12, 13]. Thence, the roles of miR-3383p involved in ovarian cancer still need more research
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