Polycystic ovary syndrome: Identification of novel and hub biomarkers in the autophagy-associated mRNA-miRNA-lncRNA network

Abstract

IntroductionPolycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder prevalent among women of reproductive age. Recent studies show that autophagy participated in the pathogenesis of PCOS, including anovulation, hyperandrogenism, and metabolic disturbances. This study was designed to screen autophagy-related genes (ATGs) that may play a pivotal role in PCOS, providing potential biomarkers and identifying new molecular subgroups for therapeutic intervention.MethodsGene expression profiles of the PCOS and control samples were obtained from the publicly available Gene Expression Omnibus database. The gene lists of ATGs from databases were integrated. Then, the weighted gene co-expression network analysis was conducted to obtain functional modules and construct a multifactorial co-expression network. Gene Ontology and KEGG pathway enrichment analyses were performed for further exploration of ATG's function in the key modules. Differentially expressed ATGs were identified and validated in external datasets with the Limma R package. To provide guidance on PCOS phenotyping, the dysfunction module consists of a co-expression network mapped to PCOS patients. A PCOS-Autophagy-related co-expression network was established using Cytoscape, followed by identifying molecular subgroups using the Limma R package. ps. RNA-sequencing analysis was used to confirm the differential expression of hub ATGs, and the diagnostic value of hub ATGs was assessed by receiver operating characteristic curve analysis.ResultsThree modules (Brown, Turquoise, and Green) in GSE8157, three modules (Blue, Red, and Green) in GSE43264, and four modules (Blue, Green, Black, and Yellow) in GSE106724 were identified to be PCOS-related by WGCNA analysis. 29 ATGs were found to be the hub genes that strongly correlated with PCOS. These hub ATGs were mainly enriched in autophagy-related functions and pathways such as autophagy, endocytosis, apoptosis, and mTOR signaling pathways. The mRNA-miRNA-lncRNA multifactorial network was successfully constructed. And three new molecular subgroups were identified via the K-means algorithm.DiscussionWe provide a novel insight into the mechanisms behind autophagy in PCOS. BRCA1, LDLR, MAP1B, hsa-miR-92b-3p, hsa-miR-20b-5p, and NEAT1 might play a considerably important role in PCOS dysfunction. As a result, new potential biomarkers can be evaluated for use in PCOS diagnosis and treatment in the future.

Bushenhuoluo Decoction improves polycystic ovary syndrome by regulating exosomal miR-30a-5p/ SOCS3/mTOR/NLRP3 signaling-mediated autophagy and pyroptosis

“…Pyroptosis and autophagy have been verified to be implicated in PCOS pathogenesis [ 27 , 28 ]. We further evaluated whether BSHLD exerted its beneficial effect through modulation of pyroptosis and autophagy.…”

CPEB1 induces autophagy and promotes apoptosis in ovarian granulosa cells of polycystic ovary syndrome

“…Autophagy is the process of maintaining cell metabolism and body function, while excessive autophagy can lead to apoptosis and tissue damage (Kumariya et al, 2021). Recent studies indicate an important role of autophagy in PCOS (Huang et al, 2022;Luo et al, 2021). Autophagy is over-activated in PCOS animals, also activated in GCs by testosterone (Hu et al, 2024;Luo et al, 2021).…”

Whispers of the polycystic ovary syndrome theater: Directing role of long noncoding RNAs

“…To unravel the mysteries of PCOS etiology, recent studies dive deep into "omics" levels [ [3] , [4] , [5] ], which focus on RNA expression arrays, protein profiles, and methylation patterns. Long noncoding RNAs (lncRNAs) are an intriguing class of transcripts that extend beyond 200 nucleotides in length and are crucial components of the noncoding genome.…”