LncRNA SNHG5 adversely governs follicular growth in PCOS via miR-92a-3p/CDKN1C axis

Area of Science:

• Reproductive biology
• Molecular endocrinology
• Genetics

Background:

• Small nucleolar RNA host genes (SNHGs) are involved in various biological processes.
• The role of SNHGs, particularly SNHG5, in polycystic ovary syndrome (PCOS) pathogenesis is not well understood.
• SNHG5 is a long non-coding RNA previously implicated in human cancers.

Purpose of the Study:

• To investigate the role of SNHG5 in the pathogenesis of PCOS.
• To explore the molecular mechanisms by which SNHG5 affects granulosa cells (GCs) in PCOS.

Main Methods:

• Analysis of SNHG5 expression in GCs from PCOS patients.
• Overexpression of SNHG5 in mouse models to induce PCOS-like phenotypes.
• In vitro studies on GC proliferation, apoptosis, and cell cycle.
• RNA sequencing (RNA-seq) to identify affected pathways.
• Investigation of the competing endogenous RNA (ceRNA) network involving SNHG5, miR-92a-3p, and CDKN1C.

Main Results:

• SNHG5 expression is elevated in GCs of women with PCOS.
• Overexpression of SNHG5 in mice recapitulated PCOS-like features.
• In vitro, SNHG5 inhibited GC proliferation, induced apoptosis, and caused G0/G1 cell-cycle arrest.
• RNA-seq revealed SNHG5 influences DNA replication and repair pathways.
• SNHG5 acts as a ceRNA for miR-92a-3p, upregulating CDKN1C expression.
• Increased CDKN1C further suppressed GC proliferation and promoted apoptosis.

Conclusions:

• SNHG5 plays a critical role in the pathogenesis of PCOS by affecting GC function.
• The SNHG5/miR-92a-3p/CDKN1C axis is a key mechanism driving PCOS.
• SNHG5 represents a potential therapeutic target for PCOS treatment.
• Further large-scale clinical studies and functional assays are needed to validate these findings.