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HAS2-AS1 是一种新型 LH/hCG 靶基因，调节 HAS2 的表达并增强卵丘细胞迁移。

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

机构信息

IVF Unit and Reproduction Laboratory, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel., 5262100, Tel Hashomer, Israel.

出版信息

J Ovarian Res. 2019 Feb 28;12(1):21. doi: 10.1186/s13048-019-0495-3.

DOI:10.1186/s13048-019-0495-3
PMID:30819231
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6396505/
Abstract

BACKGROUND

The 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.

RESULTS

HAS2-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.

CONCLUSIONS

Our 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.

摘要

背景

卵丘扩展过程是 LH 介导的排卵过程之一。透明质酸合酶 2（HAS2）调节透明质酸的合成，透明质酸是卵丘扩展过程的主要成分。最近，在我们对新的排卵相关基因的全转录组 RNA 测序中发现了长链非编码 RNA HAS2 反义 RNA 1（HAS2-AS1）。之前在不同模型中研究了 HAS2-AS1 在 HAS2 调节中的作用，但尚未在卵巢中进行研究。鉴于 HAS2-AS1 的诱导以及 HAS2 在卵丘扩展过程中的重要作用，我们假设 HAS2-AS1 在卵巢中调节 HAS2 的表达和功能。因此，我们着手研究 HAS2-AS1 在人卵巢中的表达、调节和可能的功能作用。

结果

HAS2-AS1 位于高度受我们文库调控的 HAS2 基因内。我们发现 HAS2-AS1 主要在卵丘细胞（CC）中表达。此外，HAS2-AS1 在不成熟的 CC 中表达水平较低，在成熟的 CC 中表达水平显著增加。功能研究表明，siRNA 抑制 HAS2-AS1 导致 HAS2 表达下降。此外，siRNA 抑制 HAS2-AS1 导致颗粒细胞迁移减少。

结论

我们的结果表明，HAS2-AS1 是 LH/hCG 的靶基因，它在 HAS2 表达中发挥积极作用，因此可能在调节卵丘扩展和迁移中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/2724e1dc241e/13048_2019_495_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/a4ae9a169c11/13048_2019_495_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/5a3954fefe5b/13048_2019_495_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/2724e1dc241e/13048_2019_495_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/a4ae9a169c11/13048_2019_495_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/5a3954fefe5b/13048_2019_495_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebc8/6396505/2724e1dc241e/13048_2019_495_Fig3_HTML.jpg

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