HAS2-AS1 is a novel LH/hCG target gene regulating HAS2 expression and enhancing cumulus cells migration

Yuval Yung,Micha Baum,Libby Ophir,Gil M. Yerushalmi,Ettie Maman,Ariel Hourvitz

doi:10.1186/s13048-019-0495-3

Yuval Yung, Micha Baum + Show 4 more

Open Access

https://doi.org/10.1186/s13048-019-0495-3

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Abstract

BackgroundThe cumulus expansion process is one of the LH mediated ovulatory processes. Hyaluronan synthase 2 (HAS2) regulates the synthesis of hyaluronic acid, the main component of the cumulus expansion process. Recently, the lncRNA HAS2 antisense RNA 1 (HAS2-AS1) was identified in our global transcriptome RNA-sequencing of novel ovulation associated genes. The role of HAS2-AS1 in HAS2 regulation w.as studied previously with contradictive results in different models but not in the ovary. Taken together the induction of HAS2-AS1 and the important role of HAS2 in the cumulus expansion process, we hypothesize that HAS2-AS1 regulate HAS2 expression and function in the ovary. Therefore we undertook to study the expression, regulation, and possible functional role of HAS2-AS1 in the human ovary.ResultsHAS2-AS1, located within the HAS2 gene that was highly regulated in our library. We found that HAS2-AS1 express mainly in cumulus cells (CCs). Furthermore, HAS2-AS1 showed low expression in immature CCs and a significant increase expression in mature CCs. Functional studies reveal that inhibition of HAS2-AS1 by siRNA caused decrease expression of HAS2. Furthermore, inhibition of HAS2-AS1 by siRNA results in decrease migration of granulosa cells.ConclusionsOur results suggest that HAS2-AS1 is an LH/hCG target gene that plays a positive role in HAS2 expression and thus might play a role in regulating cumulus expansion and migration.

Highlights

Critical to ovulation process is the cumulus-oocyte complex (COC) that undergos cumulus expansion
Genes that are induced following the LH surge and that are essential for proper expansion are hyaluronan synthase2 (HAS-2) and cyclooxygenase-2 (COX-2) that control the synthesis of hyaluronan and prostaglandins respectively [1, 2]
To confirm the hCG dependent expression of Hyaluronan synthase 2 (HAS2)-AS1 we compared its expression in cumulus cells (CCs) obtains from oocytes at different maturational stages

Summary

Introduction

Critical to ovulation process is the cumulus-oocyte complex (COC) that undergos cumulus expansion. HA plays a critical role in vascular pathologies as it favors cell proliferation, migration, and the development of a Protein-coding genes account for about only 2% of the human genome, whereas the vast majority of transcripts are non-coding RNAs. Recent advances in RNA-sequencing technologies have led to the discovery of thousands of previously unannotated noncoding transcripts, including many long noncoding RNAs (lncRNAs). Hyaluronan synthase 2 (HAS2) regulates the synthesis of hyaluronic acid, the main component of the cumulus expansion process. Taken together the induction of HAS2-AS1 and the important role of HAS2 in the cumulus expansion process, we hypothesize that HAS2-AS1 regulate HAS2 expression and function in the ovary. We undertook to study the expression, regulation, and possible functional role of HAS2-AS1 in the human ovary

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