Long non-coding RNA LINC-01572:28 inhibits granulosa cell growth via a decrease in p27 (Kip1) degradation in patients with polycystic ovary syndrome

Jun Zhao; Jieying Xu; Wangshen Wang; Han Zhao; Hongbin Liu; Xiaojing Liu; Jiansheng Liu; Yun Sun; Andrea Dunaif; Yanzhi Du; Zi-Jiang Chen

doi:10.1016/j.ebiom.2018.09.043

Long non-coding RNA LINC-01572:28 inhibits granulosa cell growth via a decrease in p27 (Kip1) degradation in patients with polycystic ovary syndrome

EBioMedicine. 2018 Oct:36:526-538. doi: 10.1016/j.ebiom.2018.09.043. Epub 2018 Oct 5.

Authors

Jun Zhao¹, Jieying Xu¹, Wangshen Wang¹, Han Zhao², Hongbin Liu², Xiaojing Liu¹, Jiansheng Liu¹, Yun Sun¹, Andrea Dunaif³, Yanzhi Du⁴, Zi-Jiang Chen⁵

Affiliations

¹ Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China.
² Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology(Shandong University), Ministry of Education, Shandong Provincial Clinical Medicine Research Center for reproductive health, Shandong Provincial Key Laboratory of Reproductive Medicine, No.157 Jingliu Road, Jinan 250001, China.
³ Icahn School of Medicine at Mount Sinai, Atran Bldg, 1428 Madison Ave., 4th floor, Rm 4-36, One Gustave L. Levy Place, Box 1055, New York, NY 10029, USA.
⁴ Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China. Electronic address: duyz@sjtu.edu.cn.
⁵ Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China; Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China; Center for Reproductive Medicine, Shandong Provincial Hospital, Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, The Key Laboratory for Reproductive Endocrinology(Shandong University), Ministry of Education, Shandong Provincial Clinical Medicine Research Center for reproductive health, Shandong Provincial Key Laboratory of Reproductive Medicine, No.157 Jingliu Road, Jinan 250001, China. Electronic address: chenzijiang@hotmail.com.

Abstract

Background: Disordered folliculogenesis is a key feature of polycystic ovary syndrome (PCOS), but the underlying molecular mechanism remains unclear.

Methods: Long non-coding RNA (lncRNA) expression in luteinized granulosa cells (hLGCs) derived from women with and without PCOS were analyzed using microarray and qRT-PCR. Immortalized human granulosa cell lines were cultured for proliferation assays after transfection with the LINC-01572:28 over-expression vector in the presence or absence of p27 siRNA. Protein expression analysis, rescue assays, and RNA immunoprecipitation (RIP) were used to confirm the LINC-01572:28 substrate.

Findings: LINC-01572:28 and p27 protein were elevated whereas proliferating cell nuclear antigen protein was decreased in the hLGCs of women with PCOS. LINC-01572:28 expression was positively correlated with basal testosterone levels. Over-expression of LINC-01572:28 inhibited cell proliferation and impeded G1/S transition, which were partially reversed by siRNA-mediated p27 knockdown.

Interpretation: Our findings, therefore, suggest that LINC-01572:28 suppresses cell proliferation and cell cycle progression by reducing the degradation of p27 protein via SKP2 binding.

Keywords: Granulosa cells; Polycystic ovary syndrome; Proliferation; lncRNA.

Abstract

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