The Steroidogenic Acute Regulatory Protein (StAR) Is Regulated by the H19/let-7 Axis.
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.
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.
Yi
Y
Men
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.|Reproductive Medical Center, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, P. R. China.
Yanhong
Y
Fan
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.|Department of Endocrine and Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
Yuanyuan
Y
Shen
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
Lingeng
L
Lu
Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut.
Amanda N
AN
Kallen
D000818:Animals; D002460:Cell Line; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D000098682:Steroidogenic Acute Regulatory Protein
C094335:H19 long non-coding RNA; D035683:MicroRNAs; D010750:Phosphoproteins; D062085:RNA, Long Noncoding; C487931:mirnlet7 microRNA, human; D000098682:Steroidogenic Acute Regulatory Protein