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.

miR-302s/367家族能够诱导小鼠和人类体细胞重编程为诱导多能干细胞（iPSCs），抑制几种癌细胞的增殖，甚至导致癌细胞凋亡。然而，尚未探索 miR-302s/367 家族在其他哺乳动物中的功能。在本研究中，通过将含有合成前体 miRNA 的质粒载体递送到细胞中，然后诱导成熟的 miR -302s/367 表达式。结果表明miR-302s/367不能将SFFs重编程为iPSCs；然而，它们可以通过靶向CDK2、E 2F来抑制 SFFs 的增殖和凋亡1、E 2F 2和PTEN在细胞周期和 PI3K-Akt 通路中的作用。基于我们的研究结果，提出了一种新的机制，其中 miR-302s/367 家族在哺乳动物体细胞的增殖和凋亡中发挥作用，这表明在使用 miR-302s/367 作为治疗剂时需要谨慎。