Transactivation of MicroRNA-320 by MicroRNA-383 Regulates Granulosa Cell Functions by Targeting E2F1 and SF-1 Proteins

• Published in: The Journal of biological chemistry Vol. 289; no. 26; pp. 18239 - 18257
• Main Authors: Yin, Mianmian, Wang, Xiaorong, Yao, Guidong, Lü, Mingrong, Liang, Meng, Sun, Yingpu, Sun, Fei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.06.2014; American Society for Biochemistry and Molecular Biology
• Subjects: Adult; Animals; Binding Sites; Cell Biology; Cell Proliferation; E2F Transcription Factor; E2F1 Transcription Factor - genetics; E2F1 Transcription Factor - metabolism; Estrogen; Female; Granulosa Cells - cytology; Granulosa Cells - metabolism; Humans; Mice; Mice, Inbred ICR; MicroRNA (miRNA); MicroRNAs - genetics; MicroRNAs - metabolism; Ovarian Follicle - cytology; Ovarian Follicle - growth & development; Ovarian Follicle - metabolism; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - physiopathology; Promoter Regions, Genetic; Steroidogenesis; Steroidogenic Factor 1 - genetics; Steroidogenic Factor 1 - metabolism; Transcriptional Activation; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - metabolism; Young Adult; MicroRNA (miRNA); Steroidogenesis; Cell Proliferation; E2F Transcription Factor; Estrogen
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M113.546044

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. Background: MicroRNAs are small noncoding RNAs associated with ovarian follicle development and female fertility. Results: miR-320 inhibited estradiol synthesis and proliferation of granulosa cells (GCs) through targeting E2F1 and SF-1 in vivo and in vitro. Conclusion: E2F1/SF-1 mediated miR-320-induced suppression of GC proliferation and of GC steroidogenesis. Significance: These will potentiate the usefulness of miRNA in the treatment of some steroid-related disorders.