MicroRNA-365 Inhibits Cell Growth and Promotes Apoptosis in Melanoma by Targeting BCL2 and Cyclin D1 (CCND1)

Abstract

BackgroundMicroRNA-365 (miR-365) is involved in the development of a variety of cancers. However, it remains largely unknown if and how miRNAs-365 plays a role in melanoma development.Material/MethodsIn this study, we overexpressed miR-365 in melanoma cell lines A375 and A2058, via transfection of miR-365 mimics oligos. We then investigated alterations in a series of cancer-related phenotypes, including cell viability, cell cycle, apoptosis, colony formation, and migration and invasion capacities. We also validated cyclin D1 (CCND1) and BCL2 apoptosis regulator (BCL2) as direct target genes of miR-365 by luciferase reporter assay and investigated their roles in miR-365 caused phenotypic changes. To get a more general view of miR-365’s biological functions, candidate target genes of miR-365 were retrieved via searching online databases, which were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for potential biological functions. We then analyzed The Cancer Genome Atlas (TCGA) Skin Cutaneous Melanoma (SKCM) dataset for correlation between miR-365 level and clinicopathological features of patients, and for survival of patients with high and low miR-365 levels.ResultsWe found that miR-365 was downregulated in melanoma cells. Overexpression of miR-365 remarkably suppressed cell proliferation, induced cell cycle arrest and apoptosis, and compromised the migration and invasion capacities in A375 and A2058 cell lines. We also found that the phenotypic alterations by miR-365 were partially due to downregulation of CCND1 and BCL2 oncogenes. The bioinformatics analysis revealed that predicted targets of miR-365 were widely involved in transcriptional regulation and cancer-related signaling pathways. However, analysis of SKCM dataset failed to find differences in miR-365 level among melanoma patients at different clinicopathologic stages. The Kaplan-Meier analysis also failed to discover significant differences in overall survival and disease-free survival between patients with high and low miR-365 levels.ConclusionsOur findings suggested that miR-365 might be an important novel regulator for melanoma formation and development, however, the in vivo roles in melanoma developments need further investigation.

Production of bioactive recombinant human myeloid‐derived growth factor in Escherichia coli and its mechanism on vascular endothelial cell proliferation

“…Given that the MAPK/ STAT3/cyclin D1 (encoded by the human CCND1) and PI3K signalling pathways are responsible for cell proliferation, differentiation and survival, [16][17][18][19][20] we then explained the role of MAPK/STAT3, cyclin D1 and PI3K/AKT signalling pathways in rhMYDGF-mediated HCAEC proliferation. Subsequently, we tested the bioactivity and potential mechanism of rhMYDGF in HCAECs.…”

“…Subsequently, we tested the bioactivity and potential mechanism of rhMYDGF in HCAECs. Given that the MAPK/ STAT3/cyclin D1 (encoded by the human CCND1) and PI3K signalling pathways are responsible for cell proliferation, differentiation and survival, [16][17][18][19][20] we then explained the role of MAPK/STAT3, cyclin D1 and PI3K/AKT signalling pathways in rhMYDGF-mediated HCAEC proliferation. Taken together, this study demonstrates a more economical method to produce high biologically active form of rhMYDGF, and that would be beneficial for the clinical transformation of MYDGF as a promising therapeutic molecule for the future treatment of patients with ischaemia-reperfusion injury.…”

miR‐15b enhances the proliferation and migration of lung adenocarcinoma by targeting BCL2

“…In several studies, BCL2 has been reported to act as a target gene of multiple miRNAs, including miR‐153, miR‐136 and miR‐365 . BCL2 has also been elucidated to be a target gene of miR‐15b in condylar hyperplasia and liver cancer .…”

microRNA-214 prevents traits of cutaneous squamous cell carcinoma via VEGFA and Bcl-2

“…Most importantly, miR-652-5p targeted VEGFA to suppress esophageal squamous cell carcinoma cell proliferation and metastasis [21]. On the other hand, miR-365 was found to compromised the migration and invasion, whereas enhanced apoptosis in melanoma cell lines, which was at least partially due to downregulation of the oncogene Bcl-2 [22]. miR-1290 accelerated asiatic acid-induced apoptosis through decreasing the protein expression of Bcl-2 [23].…”