Transactivation of micrornA-320 by microRNA-383 regulates granulosa cell functions by targeting E2F1 and SF-1 proteins.
Our previous studies have shown that microRNA-320 (miR-320) is one of the most down-regulated microRNAs (miRNA) in mouse ovarian granulosa cells (GCs) after TGF-β1 treatment. However, the underlying mechanisms of miR-320 involved in GC function during follicular development remain unknown. In this study, we found that pregnant mare serum gonadotropin treatment resulted in the suppression of miR-320 expression in a time-dependent manner. miR-320 was mainly expressed in GCs and oocytes of mouse ovarian follicles in follicular development. Overexpression of miR-320 inhibited estradiol synthesis and proliferation of GCs through targeting E2F1 and SF-1. E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. FSH down-regulated the expression of miR-320 and regulated the function of miR-320 in mouse GCs. miR-383 promoted the expression of miR-320 and enhanced miR-320-mediated suppression of GC proliferation. Injection of miR-320 into the ovaries of mice partially promoted the production of testosterone and progesterone but inhibited estradiol release in vivo. Moreover, the expression of miR-320 and miR-383 was up-regulated in the follicular fluid of polycystic ovarian syndrome patients, although the expression of E2F1 and SF-1 was down-regulated in GCs. These data demonstrated that miR-320 regulates the proliferation and steroid production by targeting E2F1 and SF-1 in the follicular development. Understanding the regulation of miRNA biogenesis and function in the follicular development will potentiate the usefulness of miRNA in the treatment of reproduction and some steroid-related disorders.
From the Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, the Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, and.
Mianmian
M
Yin
From the Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, the Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, and.
Xiaorong
X
Wang
the Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Guidong
G
Yao
From the Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, the Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, and.
Mingrong
M
Lü
From the Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, the Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, and.
Meng
M
Liang
the Reproductive Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China syp2008@vip.sina.com.
Yingpu
Y
Sun
From the Institute of Immunology and Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Biology, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, the Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230027, and feisun@ustc.edu.cn.
Fei
F
Sun
D000328:Adult; D000818:Animals; D001665:Binding Sites; D049109:Cell Proliferation; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011401:Promoter Regions, Genetic; D054339:Steroidogenic Factor 1 / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
D050687:E2F1 Transcription Factor; C572916:MIRN320 microRNA, human; C558685:MIRN383 microRNA, human; C577009:MIRN383 microRNA, mouse; D035683:MicroRNAs; C541056:Mirn320 microRNA, mouse; D054339:Steroidogenic Factor 1; D053773:Transforming Growth Factor beta1
Cell Proliferation; E2F Transcription Factor; Estrogen; MicroRNA (miRNA); Steroidogenesis