International Journal of Women's Health (Aug 2019)
LncRNA SRA1 may play a role in the uterine leiomyoma tumor growth regarding the MED12 mutation pattern
Abstract
Mojdeh Akbari,1 Fakhrolmolouk Yassaee,2 Mona Aminbeidokhti,1 Atieh Abedin-Do,1,3 Reza Mirfakhraie1,41Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Obstetrics and Gynecology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 3GREB, Dental Faculty, Department of Regenerative Medicine, Faculty of Medicine, Laval University, Quebec, Canada; 4Department of Molecular Genetics, Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, IranCorrespondence: Reza MirfakhraieDepartment of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar St, Velenjak Ave, Chamran highway, Tehran 19395-4719, IranTel/Fax +98 212 387 2572Email [email protected] YassaeeDepartment of Obstetrics and Gynecology, Taleghani Hospital, Shahid Beheshti University of Medical Sciences, PO Box 1985717413, Tehran, IranEmail [email protected]: Uterine leiomyomas (ULMs) are benign uterine tumors that are estrogen-dependent. Recent studies suggest that the abnormal expression of the steroid receptor RNA activator 1 (SRA1) long non-coding RNA (lncRNA) might participate in the mechanisms of tumorigenesis of some hormone-dependent tumors including breast cancer. SRA1 is known to enhance the transcriptional activity of steroid receptors and also promotes steroidogenesis. The level of steroid hormones, such as estrogen and the progesterone, and their receptors play an important role in the development and growth of leiomyoma. The aim of the present study was to determine the expression level of lncRNA SRA1 in ULM tissues considering the MED12 mutation pattern.Methods: Mutation screening was performed for MED12 exons 1 and 2 and the intronic flanking regions using Sanger sequencing in 60 ULM tissues. Quantitative real-time polymerase chain reaction (qRT-PCRs) was performed in order to estimate the expression of lncRNA SRA1 in leiomyoma samples with and without MED12 gene mutations. The expression results were analyzed by using LinReg and REST software.Results: Mutations were detected in exon 2 of the MED12 in 28 (46.67%) ULM samples; including, 21 (75%) missense mutations and 7 (25%) in-frame deletions. No mutation was detected in the MED12 exon 1. LncRNA SRA1 was over-expressed in ULM samples without MED12 mutation compared with ULM samples harboring MED12 mutation (Expression ratio=2.5, P-value=0.004).Conclusion: Present results suggest that lncRNA SRA1 may explain the phenotypic difference observed in the tumor size of ULM samples considering MED12 mutation pattern. Therefore, it serves as a good therapeutic target and provides new insight into understanding the disease molecular mechanism.Keywords: MED12, mutation, SRA1, lncRNA, uterine leiomyoma
