MiR-222 inhibits apoptosis in porcine follicular granulosa cells by targeting the THBS1 gene
MiR-222 inhibits apoptosis in porcine follicular granulosa cells by targeting the THBS1 gene
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MiR-222通过靶向THBS1基因抑制猪滤泡颗粒细胞凋亡
DOI：
10.1111/asj.13208
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发表时间：
2019
影响因子：
2
通讯作者：
Zhang Xiaodong
中科院分区：
文献类型：
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作者：
Zhu Weihua;Yang Min;Shang Jinnan;Xu Yiliang;Wang Yuanlang;Tao Qiangqiang;Zhang Liang;Ding Yueyun;Chen Yige;Zhao Dongdong;Wang Chonglong;Chu Mingxing;Yin Zongjun;Zhang Xiaodong
颗粒细胞的凋亡影响卵泡闭锁和生殖，并受到miRNAs和某些基因表达的调控。本研究旨在探讨microRNA-222（miR-222）和THBS 1在猪卵泡颗粒细胞（pGC）中的调控关系及其对细胞凋亡的影响，为开发提高猪繁殖力的方法提供实验数据。结果显示，miR-222促进pGC的增殖。miRNA模拟物和荧光素酶报告基因分析显示，miR-222在pGC中作为抗凋亡因子发挥作用。pGC中的miR-222模拟物导致抗肿瘤BCL-2基因上调、促肿瘤caspase-3基因下调和细胞凋亡抑制。miR-222抑制剂减少BCL-2，对caspase-3无显著影响。MiR-222模拟物促进雌激素水平。抑制THBS 1可抑制pGC凋亡。转染THBS 1-siRNA可降低促增殖的Bax基因。miR-222可直接靶向THBS 1基因的3′-非翻译区。miR-222模拟抑制THBS 1 mRNA和蛋白质，但这些被miR-222抑制剂上调。转染THBS 1-siRNA导致miR-222抑制剂的抑制，这表明miR-222通过靶向THBS 1抑制pGC凋亡。这些发现表明miR-222和THBS 1在卵泡闭锁、卵巢发育和女性生殖中发挥重要作用。
Apoptosis of granulosa cells affects follicular atresia and reproduction and is regulated by miRNAs and the expression of certain genes. For the present study, we investigated the regulatory relationship between microRNA‐222 (miR‐222) andTHBS1in porcine follicular granulosa cells (pGCs) and its effects on apoptosis to provide empirical data for developing methods to improve pig fecundity. Results revealed that miR‐222 promotes the proliferation of pGCs. MiRNA mimics and luciferase reporter assays revealed that miR‐222 functions as an anti‐apoptotic factor in pGCs. MiR‐222 mimics in pGCs result in the upregulation of the anti‐apoptoticBCL‐2gene, down‐regulation of the proapoptoticcaspase‐3gene, and inhibition of apoptosis. MiR‐222 inhibitors reducedBCL‐2and had no significant effect oncaspase‐3. MiR‐222 mimics promoted estrogen levels. Inhibition ofTHBS1inhibited pGC apoptosis. Transfection ofTHBS1‐siRNA reduced the proapoptoticBAXgene. MiR‐222 can directly target the 3′‐untranslated region of theTHBS1gene. MiR‐222 mimics suppressedTHBS1mRNA and proteins, but these were upregulated by the miR‐222 inhibitor. Transfection ofTHBS1‐siRNA resulted in the inhibition of the miR‐222 inhibitor, which suggests that miR‐222 inhibits pGC apoptosis by targetingTHBS1. These findings suggest that miR‐222 andTHBS1play important roles in follicular atresia, ovarian development, and female reproduction.