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MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic ? cells.

ABSTRACT: MicroRNAs (miRNAs) have been implicated in ? cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in ? cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on ? cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated ? cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, ? cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic ? cells as well as a potential functional regulation factor in islet endothelial cells.

SUBMITTER: Shen Z

PROVIDER: S-EPMC6428088 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic β cells.

Shen Ziyang Z Jiang Hemin H Hsu Hsiang-Ting HT Qian Li L Fu Qi Q Shen Min M Chen Shu S Yang Tao T

Aging 20190301 5

MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferatio ...[more]

PMID: 30822278

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Project description:MicroRNA (miR) are a class of small non-coding RNA that are able to inhibit gene expression by directly binding to the 3' untranslated region (UTR) of their target mRNA and thus promote translational repression or mRNA degradation. Recently, miR-9 was reported to have a suppressive role in malignant melanoma; however, the underlying mechanism remains largely unclear. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to examine the mRNA and protein expression levels in malignant melanoma tissues and cell lines. The MTT assay and wound healing assay were used to examine the cell viability, proliferation and migratory capacities. Bioinformatics prediction and luciferase reporter assay were performed to investigate the relationship between miR-9 and its potential target gene. The present data revealed that miR-9 expression was significantly downregulated in malignant melanoma tissues when compared with their matched adjacent non-tumor tissues. Furthermore, the expression levels of miR-9 were reduced in malignant melanoma cell lines when compared with human normal skin HACAT cells. Moreover, the ectopic expression of miR-9 significantly suppressed the proliferation and migration of malignant melanoma cells, accompanied with a remarkable decrease in the protein expression levels of sirtuin 1 (SIRT1), which were markedly upregulated in malignant melanoma tissues and cell lines. Additionally, restoration of SIRT1 reversed the suppressive effects of miR-9 on the proliferation and migration of malignant melanoma cells. Luciferase reporter assay data further identified SIRT1 as a direct target gene of miR-9. To conclude, the present findings indicate that miR-9 has a suppressive role in malignant melanoma cell viability and migration, at least in part, via directly inhibiting the protein expression of its target gene, SIRT1. Therefore, miR-9 may serve as a potential candidate for the treatment of malignant melanoma.

Dataset Information

MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic ? cells.

Publications

MicroRNA-127 inhibits cell proliferation via targeting Kif3b in pancreatic β cells.

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