Long noncoding RNA HUPCOS promotes follicular fluid androgen excess in PCOS patients via aromatase inhibition.

CONTEXT: Androgen excess is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear. OBJECTIVE: To determine the role and mechanism of novel long noncoding RNA (lncRNA) highly up-regulated in PCOS (HUPCOS) in the androgen excess of PCOS patients. DESIGN: The lncRNA expression profile in granulosa cells derived from PCOS and non-PCOS women were analyzed by using microarray assay. Human granulosa cell line KGN was used for mechanism investigation. SETTING: This was a university-based study. PATIENTS: Thirty-eight PCOS and 38 control patients were recruited: 8 PCOS and 8 control samples used for microarray discovery, the remaining 30 PCOS cases and 30 controls for quantitative RT-PCR validation. MAIN OUTCOME MEASURES: The aberrant expression lncRNA profile of PCOS patients was measured using microarray. The relationship of HUPCOS and follicular fluid testosterone was measured. Aromatase expression were analyzed after HUPCOS downregulation. HUPCOS interaction protein was confirmed by RNA pull-down. RESULTS: The significantly elevated lncRNA in PCOS granulosa cells was named HUPCOS, which was positively correlated with follicular fluid testosterone of PCOS patients. HUPCOS downregulation increased aromatase expression and promoted conversion of androgen to estrogen. RNA-binding protein with multiple splicing (RBPMS) was the most likely protein that combined with HUPCOS. CONCLUSIONS: Our findings suggested that HUPCOS mediated androgen excess in follicular fluid of PCOS patients by suppressing aromatase expression via interaction with RBPMS.