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Biosci Rep. 2019 Jun 28;39(6). pii: BSR20190066. doi: 10.1042/BSR20190066. Print 2019 Jun 28.

MiR-876-5p regulates gastric cancer cell proliferation, apoptosis and migration through targeting WNT5A and MITF.

Author information

1
Department of Gastroenterology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518000, Guangdong, China.
2
Department of Gastroenterology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518000, Guangdong, China LishengWang_wls_2@163.com YingcaiHongvip@163.com.
3
Department of Thoracic Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen 518000, Guangdong, China LishengWang_wls_2@163.com YingcaiHongvip@163.com.

Abstract

MicroRNAs (miRNAs) are reported to play critical roles in various cancers. Recently, mounting miRNAs are found to exert oncogenic or tumor inhibitory role in gastric cancer (GC), however, their potential molecular mechanism in GC remains ill-defined. Currently, we aimed to elucidate the functional and mechanistic impacts of a novel miRNA on GC cellular process. The significant down-regulation of miR-876-5p in GC cells attracted our attention. In function, we performed gain-of-function assays and found that miR-876-5p overexpression repressed proliferative, anti-apoptotic and migratory abilities and epithelial-mesenchymal transition (EMT) of GC cells. By applying bioinformatics prediction and mechanism experiments, we verified that miR-876-5p could double-bind to the 3' untranslated regions (3'UTRs) of Wnt family member 5A (WNT5A) and melanogenesis associated transcription factor (MITF), thus regulating their mRNA and protein levels. Both WNT5A and MITF were highly expressed in GC cells. Additionally, we conducted loss-of-function assays and confirmed the oncogenic roles of WNT5A and MITF in GC. Finally, rescue assay uncovered a fact that miR-876-5p suppressed GC cell viability and migration, but induced cell apoptosis via targeting WNT5A and MITF. Taken together, we might offer a valuable evidence for miR-876-5p role in GC development.

KEYWORDS:

MITF; WNT5A; gastric cancer; miR-876-5p

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