CREB1 Is Involved in miR-134-5p-Mediated Endometrial Stromal Cell Proliferation, Apoptosis, and Autophagy.
CREB1 Is Involved in miR-134-5p-Mediated Endometrial Stromal Cell Proliferation, Apoptosis, and Autophagy.
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作者：
子宫内膜容受性的成功建立是保证母羊生育力和经济效益的关键因素。湖羊因其繁殖力高、常年发情而备受关注。本研究发现，在黄体期，高生育力湖羊的子宫腺密度、子宫系数和子宫肉阜数均高于低生育力湖羊。利用RNA测序技术（RNA-Seq）在不同生育力湖羊子宫内膜中鉴定出数千个差异表达基因。利用生物信息学分析筛选出与子宫内膜容受性相关的基因。qRT-PCR分析进一步揭示了cAMP反应元件结合蛋白1（CREB 1）在湖羊发情周期子宫内膜中的差异表达。在功能上，我们的研究结果表明，CREB 1显着影响子宫内膜容受性标记基因的表达水平，促进细胞增殖，促进从G1期到S期的过渡，并抑制细胞凋亡和自噬。此外，我们观察到miR-134- 5 p和CREB 1在子宫内膜中呈负线性相关。此外，CREB 1过表达阻止了miR-134- 5 p对子宫内膜基质细胞（ESC）生长的负面影响。综上所述，这些数据表明CREB 1受miR-134- 5 p调控，并可能通过调节ESCs的功能促进子宫容受性的建立。此外，本研究还为鉴定与育性相关的候选基因提供了新的理论参考。
The successful establishment of endometrial receptivity is a key factor in ensuring the fertility of ewes and their economic benefits. Hu sheep have attracted attention due to their high fecundity and year-round estrus. In this study, we found that in the luteal phase, the uterine gland density, uterine coefficient, and number of uterine caruncles of high-fertility Hu sheep were higher than those of low-fertility Hu sheep. Thousands of differentially expressed genes were identified in the endometrium of Hu sheep with different fertility potential using RNA sequencing (RNA-Seq). Several genes involved in endometrial receptivity were screened using bioinformatics analysis. The qRT-PCR analysis further revealed the differential expression of cAMP reactive element binding protein-1 (CREB1) in the Hu sheep endometrium during the estrous cycle. Functionally, our results suggested that CREB1 significantly affected the expression level of endometrial receptivity marker genes, promoted cell proliferation by facilitating the transition from the G1 phase to the S phase, and inhibited cell apoptosis and autophagy. Moreover, we observed a negative linear correlation between miR-134-5p and CREB1 in the endometrium. In addition, CREB1 overexpression prevented the negative effect of miR-134-5p on endometrial stromal cell (ESC) growth. Taken together, these data indicated that CREB1 was regulated by miR-134-5p and may promote the establishment of uterine receptivity by regulating the function of ESCs. Moreover, this study provides new theoretical references for identifying candidate genes associated with fertility.
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DOI：
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