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.
Highlights
As one of the most frequent cancerous occurring in both male and female, gastric cancer (GC) is ranked third in cancer-related mortality all around the world [1,2]
Results indicated that only miR-876-5p was significantly down-regulated in GC cells compared with the normal human gastric epithelial cell line GES-1 (Figure 1A)
Cell Counting Kit-8 (CCK-8) and ethynyl-2 -deoxyuridine (EdU) assays indicated that the miR-876-5p up-regulation significantly reduced MGC803 and MKN-45 cell viability compared with control groups (Figure 1C,D)
Summary
As one of the most frequent cancerous occurring in both male and female, gastric cancer (GC) is ranked third in cancer-related mortality all around the world [1,2]. In spite of great advances in surgical and comprehensive therapies, the clinical effect of GC patients remains to be improved [5,6]. It is well-known that genetic and epigenetic dysregulations are implicated in GC onset and progression [7,8]. Copious reports reveal that miRNAs are widely involved in various cancerous biological behaviors and pathological processes, including GC [10,11,12]. Compelling evidence has indicated that miRNA is emerging as an indispensable modulator of cellular process, including cell proliferation, migration, apoptosis, differentiation, angiogenesis and immune response in various human diseases, especially human cancers
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