Abstract
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, E2F1, E2F2, 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.
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This work was supported by the National Natural Science Foundation of China [Grant Number: 31660340]; Natural Science Foundation of Inner Mongolia Autonomous Region of China [Grant Number: 2018MS03062].
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XW conducted most of the experiments and analyzed the data. RT, XC, and XJ conducted some of experiments. XH contributed to the conception of the study. LM designed the study, wrote and submitted the manuscript.
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Wu, X., Tong, R., Chen, X. et al. The miR-302s/367 Cluster Inhibits the Proliferation and Apoptosis in Sheep Fetal Fibroblasts via the Cell Cycle and PI3K-Akt Pathways. Mamm Genome 32, 183–194 (2021). https://doi.org/10.1007/s00335-021-09873-5
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DOI: https://doi.org/10.1007/s00335-021-09873-5