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

Jun Zhao1, Jieying Xu1, Wangshen Wang1

  • 1Center 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.

Ebiomedicine
|October 9, 2018
PubMed
Abstract

Insights

Polycystic ovary syndrome (PCOS) involves disordered folliculogenesis. This study found that LINC-01572:28, elevated in PCOS, inhibits granulosa cell proliferation by stabilizing p27 protein.

Area of Science:

  • Reproductive biology
  • Molecular endocrinology
  • Genetics

Background:

  • Polycystic ovary syndrome (PCOS) is characterized by disordered folliculogenesis, with unclear molecular mechanisms.
  • Granulosa cell dysfunction is implicated in PCOS pathogenesis.

Purpose of the Study:

  • To investigate the role of long non-coding RNA (lncRNA) LINC-01572:28 in PCOS-related disordered folliculogenesis.
  • To elucidate the molecular mechanism by which LINC-01572:28 affects granulosa cell function.

Main Methods:

  • Microarray and qRT-PCR analysis of lncRNA expression in human luteinized granulosa cells (hLGCs) from women with and without PCOS.
  • Cell proliferation assays, Western blotting, and RNA immunoprecipitation (RIP) in immortalized granulosa cell lines.
  • Manipulation of LINC-01572:28 and p27 expression using overexpression vectors and siRNA.

Main Results:

  • LINC-01572:28 and p27 protein levels were elevated in hLGCs from women with PCOS.
  • Overexpression of LINC-01572:28 inhibited hLGC proliferation and G1/S cell cycle transition.
  • LINC-01572:28 overexpression led to decreased degradation of p27 protein, partially reversed by p27 knockdown.

Conclusions:

  • LINC-01572:28 plays a significant role in suppressing granulosa cell proliferation and cell cycle progression in PCOS.
  • The mechanism involves LINC-01572:28 reducing p27 protein degradation through binding to SKP2.
  • LINC-01572:28 represents a potential therapeutic target for PCOS.

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