Effect of lncRNA MALAT1 on the Granulosa Cell Proliferation and Pregnancy Outcome in Patients With PCOS

Abstract

Follicle arrest is one of the main characteristics of polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductive-aged women. Increasing evidence proves that high anti-Mullerian hormone (AMH) levels may play an important role in follicular development. Long noncoding RNA (lncRNA) with a length of more than 200 nt is widely involved in the directional differentiation, growth, and development of cells, whereas whether lncRNA is involved in AMH’s role in follicular development is unknown. In this study, we analyzed lncRNA expression in ovarian granulosa cells (GCs) collected from women with and without PCOS via high-throughput sequencing. The results showed that a total of 79 noncoding transcripts were differently expressed in GCs of PCOS patients, including upregulated lncRNA MALAT1. The upregulation of MALAT1 was further confirmed by RT-qPCR in GCs from a larger cohort of PCOS patients. Furthermore, knockdown MALAT1 can promote the proliferation of KGN cell in vitro. These data suggested a role for MALAT1 in the development of PCOS. Meanwhile, MALAT1 and phosphorylated SMAD 1/5 (Ser463/465) protein were upregulated in KGN cells after exogenous AMH stimulation, which identified AMH perhaps as a regulator for the expression of MALAT1. We also found that MALAT1 can predict clinical pregnancy outcome to a certain extent by ROC curve analysis (area: 0.771, p = 0.007, 95% CI: 0.617–0.925, sensitivity: 57.1%, specificity: 91.7%). Thus, our findings revealed a role of lncRNA MALAT1 in inhibiting granulosa cell proliferation and may be correlated with pregnancy outcome in PCOS.

Transcriptome analysis identification of A-to-I RNA editing in granulosa cells associated with PCOS

“…The dataset GSE138518 retrieved from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo) database was used for RNA editing event discovery and consisted of GCs from adult women, including five with PCOS and six controls without PCOS undergoing in vitro fertilization treatments (IVF) (12). In addition, the validation dataset PRJNA762274 was retrieved from the European Nucleotide Archive Databank (https://www.ebi.ac.uk/), which contained GCs from four PCOS patients and four controls undergoing IVF or intracytoplasmic sperm injection (13). The processes of RNA extraction, library construction, and RNA sequencing were described in the original studies.…”

“…To validate the common characteristics of RNA editing, we conducted a comparative analysis using another PCOS and control GC sample dataset (PRJNA762274) from an independent study (13). By using the same analysis procedure, we identified the differential editing sites shown in Supplementary Table S3.…”

Modulation of the Inflammatory Response in Polycystic Ovary Syndrome (PCOS)—Searching for Epigenetic Factors

“…The results of the latest research show a significant impact of ncRNAs on the processes related to inflammation and immune response in PCOS. It was demonstrated that a total of 79 noncoding transcripts were differentially expressed in the GCs of PCOS patients [ 71 , 123 ]. For example, an 8.7 kb long ncRNA, long-chain noncoding RNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1), has been found to interact with miRNAs in ovarian granulosa cells (GCs).…”