Men Yi, Fan Yanhong, Shen Yuanyuan, Lu Lingeng, Kallen Amanda N
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Department of Head and Neck Surgery, State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Endocrinology. 2017 Feb 1;158(2):402-409. doi: 10.1210/en.2016-1340.
The steroidogenic acute regulatory protein (StAR) governs the rate-limiting step in steroidogenesis, and its expression varies depending on the needs of the specific tissue. Tight control of steroid production is essential for multiple processes involved in reproduction, including follicular development, ovulation, and endometrial synchronization. Recently, there has been a growing interest in the role of noncoding RNAs in the regulation of reproduction. Here we demonstrate that StAR is a novel target of the microRNA let-7, which itself is regulated by the long noncoding RNA (lncRNA) H19. Using human and murine cell lines, we show that overexpression of H19 stimulates StAR expression by antagonizing let-7, which inhibits StAR at the post-transcriptional level. Our results uncover a novel mechanism underlying the regulation of StAR expression and represent the first example of lncRNA-mediated control of the rate-limiting step of steroidogenesis. This work thus adds to the body of literature describing the multiple roles in oncogenesis, cellular growth, glucose metabolism, and now regulation of steroidogenesis, of this complex lncRNA.
类固醇生成急性调节蛋白（StAR）控制着类固醇生成中的限速步骤，其表达因特定组织的需求而异。严格控制类固醇生成对于生殖涉及的多个过程至关重要，包括卵泡发育、排卵和子宫内膜同步。最近，非编码RNA在生殖调节中的作用越来越受到关注。在这里，我们证明StAR是微小RNA let-7的一个新靶点，而let-7本身受长链非编码RNA（lncRNA）H19的调控。利用人和小鼠细胞系，我们表明H19的过表达通过拮抗let-7来刺激StAR表达，let-7在转录后水平抑制StAR。我们的结果揭示了StAR表达调控的一种新机制，并且代表了lncRNA介导控制类固醇生成限速步骤的首个例子。因此，这项工作为描述这种复杂lncRNA在肿瘤发生、细胞生长、葡萄糖代谢以及现在的类固醇生成调节中的多种作用的文献增添了内容。
