LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes

Asmaa A ElMonier; Noha A El-Boghdady; Sally A Fahim; Dina Sabry; Khaled A Elsetohy; Amira A Shaheen

doi:10.1016/j.ncrna.2023.02.008

LncRNA NEAT1 and MALAT1 are involved in polycystic ovary syndrome pathogenesis by functioning as competing endogenous RNAs to control the expression of PCOS-related target genes

Noncoding RNA Res. 2023 Mar 3;8(2):263-271. doi: 10.1016/j.ncrna.2023.02.008. eCollection 2023 Jun.

Authors

Asmaa A ElMonier¹, Noha A El-Boghdady¹, Sally A Fahim², Dina Sabry^{3

4}, Khaled A Elsetohy⁵, Amira A Shaheen¹

Affiliations

¹ Department of Biochemistry, Faculty of Pharmacy, Cairo University, 11562, Cairo, Egypt.
² Department of Biochemistry, School of Pharmacy, Newgiza University (NGU), Newgiza, Km 22 Cairo-Alexandria Desert Road, 12577, Giza, Egypt.
³ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Badr University in Cairo, 11562, Cairo, Egypt.
⁴ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, 12613, Cairo, Egypt.
⁵ Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, 12111, Cairo, Egypt.

Abstract

Accumulating evidence has shown an abnormal expression of several non-coding RNAs in ovarian tissues which might be closely linked with the pathogenesis of PCOS. The aim of this study was to identify competing endogenous (ce) RNA network: long non-coding RNA (lncRNA), microRNA (miRNA) and their target genes: androgen receptor (AR), follistatin (FST) and insulin receptor substrate-2 (IRS-2), which are relevant to PCOS, to underline the molecular pathogenesis of PCOS and assist in early diagnosis and treatment. Bioinformatic analysis was performed to retrieve a ceRNA network: [lncRNA (NEAT1 and MALAT1) - miRNA (miR-30a-5p and miR-30d-5p) - mRNA (AR, FST and IRS-2)] linked to PCOS. Expression of the selected RNAs was examined by qPCR in peripheral blood leukocytes obtained from 73 PCOS patients (41 obese and 32 non-obese) and 31 healthy controls. PCOS patients showed significantly higher expression levels of NEAT1, miR-30a-5p, AR, FST and IRS-2, with significantly lower expression levels of MALAT1 and miR-30d-5p relative to controls especially in obese versus non-obese patients. Receiver operating characteristic (ROC) curve analysis indicated that most of the selected RNAs could serve as potential early diagnostic markers for PCOS with the highest efficiency obtained upon combining NEAT1 and miR-30d-5p or MALAT1 and miR-30a-5p with either of PCOS target genes. Moreover, all addressed RNAs had been proved as potential predictors of PCOS. The obtained data of ceRNA network raised the possibility that NEAT1 overexpression may increase the expression levels of AR, FST and IRS-2 by sponging miR-30d-5p, while low expression of MALAT1 may allow higher expression of the above genes via increasing miR-30a-5p, suggesting their involvement in PCOS pathogenesis and promising role for future diagnosis and targeted therapy.

Keywords: Androgen receptor; Follistatin and insulin receptor substrate-2; MALAT1; NEAT1; Polycystic ovary syndrome.