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

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

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.

Original languageEnglish
Pages (from-to)526-538
Number of pages13
JournaleBioMedicine
Volume36
DOIs
StatePublished - Oct 2018

Keywords

  • Granulosa cells
  • Polycystic ovary syndrome
  • Proliferation
  • lncRNA

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