title: Downregulation of microRNA‑146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin‑1 receptor‑associated kinase and tumor necrosis factor receptor‑associated factor 6.
abstract: Premature ovarian failure (POF), an ovarian disorder of multifactorial origin, is defined as the occurrence of amenorrhea, hypergonadotropism and hypoestrogenism in females <40 years old. Apoptosis of ovarian granulosa cells is important in POF and understanding the regulatory mechanism underlying ovarian granulosa cell apoptosis may be beneficial for the management of POF. Increasing evidence suggests that microRNAs (miRs) have a regulatory function in oocyte maturation and ovarian follicular development. In the present study, the expression of miR‑146a in plasma and ovarian granulosa cells obtained from patients with POF, its effect on the apoptosis of ovarian granulosa cells and the possible underlying mechanisms were examined. The present study demonstrated that compared with the control groups, the expression of miR‑146a in the plasma and in ovarian granulosa cells of patients with POF was significantly upregulated. Furthermore, it was found that miR‑146a simultaneously targeted interleukin‑1 receptor‑associated kinase (IRAK1) and tumor necrosis factor receptor‑associated factor 6 (TRAF6), which regulated the activity of nuclear factor‑κB and IκBα. In addition, the results demonstrated that inhibition of the caspase cascade by caspase inhibitors attenuated the effects of miR‑146a on ovarian granulosa cell apoptosis. Taken together, these results suggest that miR‑146a has an important promoting effect on the apoptosis of granulosa cells by targeting IRAK1 and TRAF6 via the caspase cascade pathway. These results may be useful for the management of POF.
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Mingxuan
authors.initials: M
authors.lastname: Xie
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Da
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Geriatric Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Shi
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006107:Granulosa Cells / Q000378:metabolism*; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D016649:Primary Ovarian Insufficiency / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics*; D015854:Up-Regulation
chemical_list: C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D048029:TNF Receptor-Associated Factor 6; D053592:Interleukin-1 Receptor-Associated Kinases; D020169:Caspases