LncRNA PKD1P6 modulates ovarian granulosa cell survival of hyperandrogenic polycystic ovary syndrome by targeting miR-135b-5p and inhibiting ERK1/2 signaling
Weidong Zhou,
Yikai Lian,
Jiahao Chen,
Teng Zhang,
Wenjing Zhang,
Ruofan Huang,
Mengjie Yang,
Xiaohong Yan,
Qionghua Chen
Affiliations
Weidong Zhou
Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China; Corresponding author.
Yikai Lian
Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Jiahao Chen
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Teng Zhang
Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Wenjing Zhang
Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Ruofan Huang
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Mengjie Yang
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Xiaohong Yan
Reproductive Medicine Center, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
Qionghua Chen
Department of Obstetrics and Gynecology, the First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China; Corresponding author.
Polycystic ovary syndrome (PCOS) is the most common and multifactorial endocrine disease among women of reproductive age. Aberrant folliculogenesis is a common pathological characteristic of PCOS, but the underlying molecular mechanism remains unclear. Emerging evidence indicated that aberrant expression of long noncoding RNAs (lncRNAs) may contribute to the pathogenesis of PCOS. In this study, we found that lncRNA PKD1P6 expression was remarkably down-regulated in ovarian granulosa cells (GCs) of hyperandrogenic PCOS (HA-PCOS) patients and negatively correlated with serum testosterone (T) levels. We further showed that overexpression of PKD1P6 markedly reduced cell viability, attenuated DNA synthesis capacity, arrested the cell cycle at G0/G1 phase and promoted apoptosis of KGN cells. Exosomes derived from PKD1P6 overexpression cells exerted similar effects to PKD1P6 overexpression on the function of KGN cells. Mechanistically, PKD1P6 could act as a competing endogenous RNA (ceRNA) by directly binding with miR-135b-5p. Overexpression of PKD1P6 significantly suppressed ERK1/2 activation, whereas up-regulation of miR-135b-5p exerted an opposing effect. Additionally, excessive androgen was showed to diminish PKD1P6 expression while promote miR-135b-5p expression of PCOS models in vitro and vivo. Collectively, our findings delineate the clinical significance of PKD1P6 in HA-PCOS and the new regulatory mechanisms involved in abnormal folliculogenesis, providing a promising therapeutic target for HA-PCOS.
