The miR-302s/367 Cluster Inhibits the Proliferation and Apoptosis in Sheep Fetal Fibroblasts via the Cell Cycle and PI3K-Akt Pathways

The miR-302s/367 family has the ability to induce mouse and human somatic cell reprogramming into induced pluripotent stem cells (iPSCs), inhibit the proliferation of several types of cancer cells, and even cause cancer cell apoptosis. However, the functions of the miR-302s/367 family in other mamma...

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Bibliographic Details
Published in:Mammalian genome 2021-06, Vol.32 (3), p.183-194
Main Authors: Wu, Xian, Tong, Ruiying, Chen, Xiuli, Jiang, Xinying, He, Xiaoying, Ma, Libing
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Animal Genetics and Genomics
Animals
Apoptosis
Apoptosis - genetics
Biomedical and Life Sciences
Cell Biology
Cell cycle
Cell Cycle - genetics
Cell proliferation
Cell Proliferation - genetics
Cyclin-dependent kinase 2
Fetus - metabolism
Fetuses
Fibroblasts
Fibroblasts - metabolism
Fibroblasts - pathology
Human Genetics
Humans
Inhibitory postsynaptic potentials
Life Sciences
Mice
MicroRNAs - genetics
Oncogene Protein v-akt - genetics
Phosphatidylinositol 3-Kinases - genetics
Pluripotency
PTEN protein
Sheep - genetics
Signal Transduction - immunology
Somatic cells
Stem cell transplantation
Stem cells
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Summary:The miR-302s/367 family has the ability to induce mouse and human somatic cell reprogramming into induced pluripotent stem cells (iPSCs), inhibit the proliferation of several types of cancer cells, and even cause cancer cell apoptosis. However, the functions of the miR-302s/367 family in other mammals have not been explored. In the present study, the effects of miR-302s/367 on reprogramming, proliferation, and apoptosis in sheep fetal fibroblasts (SFFs) were evaluated by the delivery of a plasmid vector containing synthetic precursor miRNAs into cells, followed by the induction of mature miR-302s/367 expression. The results showed that miR-302s/367 could not reprogram SFFs into iPSCs; however, they could inhibit both the proliferation and apoptosis of SFFs by targeting CDK2 , E 2F 1 , E 2F 2 , and PTEN in the cell cycle and PI3K-Akt pathways. Based on our findings, a novel mechanism was proposed in which the miR-302s/367 family functions in both the proliferation and apoptosis of somatic cells in mammals, suggesting that caution is needed when using miR-302s/367 as therapeutic agent.
ISSN:0938-8990
1432-1777
DOI:10.1007/s00335-021-09873-5