MiR-142 suppresses progression of gastric carcinoma via directly targeting LRP8

Recently, the role of miRNA-142 (miR-142) in tumor development has attracted extensive attention. The aim of this study was to investigate the impact of miR-142 and its potential target low-density lipoprotein receptor (LDLR)-related protein 8 (LRP8) on the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of gastric carcinoma (GC). Gene and protein expressions were detected using RT-qPCR and Western blotting, respectively. The biological behaviors of GC cell lines were determined by CCK-8, flow cytometry and Transwell assays, respectively. The interaction between miR-142 and LRP8 was confirmed with dual luciferase reporter assay. Xenograft nude mouse model was used to observe tumor growth. Here, miR-142 expression was markedly reduced in GC tissues and cells, and was negatively correlated with lymph node metastasis and poor prognosis in patients with GC. Stable miR-142 overexpression was sufficient to inhibit cell proliferation, migration and invasion in vitro and reduce tumor growth in vivo, accompanied by increased expression of the epithelial marker and reduced levels of mesenchymal markers. Mechanistically, the 3'-untranslated regions (3'-UTR) of LRP8 was a direct target of miR-142. Restoration of LRP8 attenuated the inhibitory effect of miR-142 on GC cells, whereas inhibition of LRP8 caused the opposite outcomes. In conclusion, our findings suggest that miR-142 plays a significant role in suppressing progression of GC by targeting LRP8, and miR-142 may be useful for the development of novel targeted therapies. (C) 2020 Elsevier Masson SAS. All rights reserved.