The long non-coding RNA BBOX1 antisense RNA 1 is upregulated in polycystic ovary syndrome (PCOS) and suppresses the role of microRNA-19b in the proliferation of ovarian granulose cells

Abstract

Abstract Background MicroRNA-19b (miR-19b) has been reported to be downregulated in polycystic ovary syndrome (PCOS), while its upstream regulators are unclear. We speculated that miR-19b could potentially form a binding relationship with BBOX1 antisense RNA 1 (BBOX1-AS1), a long non-coding RNA recognized for its critical role in ovarian cancer. Subsequently, we investigated into their interaction in PCOS. Methods The expression of miR-19b and BBOX1-AS1 in follicular fluid from both control women (n = 80) and women with PCOS (n = 80) was detected by RT-qPCR. Correlations were analyzed with Pearson’ correlation coefficient. The binding of miR-19b to the wild-type (-wt) ad mutant (-mut) BBOX1-AS1 was determined by RNA-RNA pulldown assay. Their interactions were detected by overexpression assay. Bromodeoxyuridine (BrdU) assay was applied for proliferation analysis. Results BBOX1-AS1 was highly upregulated, while miR-19b was downregulated in PCOS. There was no close correlation across PCOS and the control samples. Consistently, they did not regulate the expression of each other in granulosa cells. However, BBOX1-AS1-wt, but not BBOX1-AS1-mut, could directly interact with miR-19b. BBOX1-AS1 suppressed the role of miR-19b in inhibiting granulosa cell proliferation. Conclusion BBOX1-AS1 is highly upregulated in PCOS, and it may serve as an endogenous competing RNA for miR-19b to suppress its role in inhibiting granulosa cell proliferation. Our study suggested the role of BBOX1-AS1 as a potential target to treat PCOS.

Keywords

• Polycystic ovary syndrome
• miR-19b
• BBOX1-AS1
• Granulosa cell proliferation