CDKN2B-AS1 is overexpressed in polycystic ovary syndrome and sponges miR-181a to promote granulosa cell proliferation

Abstract

MiR-181a suppresses the proliferation of mouse granulosa cells, which participate in polycystic ovary syndrome (PCOS), suggesting the potential role of miR-181a in PCOS. Our bioinformatics analysis revealed that miR-181a could bind CDKN2B-AS1, a lncRNA regulates ovarian endometriosis. This research was, therefore, conducted to explore the potential crosstalk between CDKN2B-AS1 and miR-181a in PCOS. Expression analysis of CDKN2B-AS1 and miR-181a in follicular fluid from 60 PCOS patients and 60 controls was done with reverse transcriptions-quantitative PCRs. The direct interaction between CDKN2B-AS1 and miR-181a was predicted by IntaRNA and confirmed by RNA pull-down assay. CDKN2B-AS1 in nuclear and cytoplasm of granulosa cells was detected by cellular fractionation assay. The role of CDKN2B-AS1 and miR-181a in granulosa cell proliferation was analyzed by 5-bromodeoxyuridinc assay. In this study, CDKN2B-AS1 was expressed in high amounts in PCOS, whereas miR-181a was downregulated in PCOS, CDKN2B-AS1 was detected in both nucleus and cytoplasm. Although CDKN2B-AS1 and miR-181a were not closely correlated, CDKN2B-AS1 directly interacted with miR-181a. CDKN2B-AS1 and miR-181a overexpression failed to affect the expression of each other. In addition, the inhibitory effect of miR-181a on granulosa cell proliferation was attenuated by CDKN2B-AS1. CDKN2B-AS1 is overexpressed in PCOS and may sponge miR-181a to promote granulosa cell proliferation. Our study characterized a novel CDKN2B-AS1/miR-181a pathway in PCOS. This novel pathway may serve as a potential target to treat PCOS.

Whispers of the polycystic ovary syndrome theater: Directing role of long noncoding RNAs

“…Likewise, HAS2 antisense RNA 1 downregulated TGFβ signaling by inducing hypermethylation of the TGFBR2 promoter region, which aggravated the pathological processes in PCOS [ 25 ]. BBOX1-AS1 and CDKN2B-AS1 were found to be highly upregulated in PCOS and may serve as ceRNAs for miR-19b and miR-181a, respectively, to promote GC proliferation [ 26 , 27 ]. Furthermore, the lncRNA X-inactive specific transcript reportedly plays a critical role in PCOS by modulating the miR-30c-5p/BCL2L11 signaling axis and regulating the physiology of GCs [ 28 ].…”

“… [ 5 ] Human GCs CDKN2B-AS1(Cyclin dependent kinase inhibitor 2B-AS1) Up CDKN2B-AS1 is overexpressed in PCOS and may sponge miR-181a to promote granulosa cell proliferation. [ 27 ] Human serum CTBP1-AS (C-Terminal binding protein 1 antisense) Up Abnormal CTBP1-AS expression is a risk factor for PCOS and it is a predictor of variability in serum total testosterone level in Chinese women with PCOS. [ 54 ] Human serum ENST00000550337.1 Up Patients with elevated lncRNA ENST00000550337.1 expression had significantly increased PCOS risk after adjusting for age and BMI.…”