Construction and analysis of a lncRNA ( PWRN2 )-mediated ceRNA network reveal its potential roles in oocyte nuclear maturation of patients with PCOS

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Abstract

Background

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in women. An lncRNA, namely, Prader-Willi region nonprotein coding RNA 2 ( PWRN2), was up-regulated in the cumulus cells of patients with PCOS. However, the molecular mechanism of PWRN2 in PCOS remains largely unknown.

Methods

In this study, the expression levels of PWRN2 were tested in cumulus cells through qRT-PCR analysis to confirm its potential roles in oocyte nuclear maturation of PCOS. A PWRN2-mediated ceRNA network was constructed based on three microarray datasets to investigate the molecular mechanism of PWRN2 in oocyte development of patients with PCOS. The direct interactions of the candidate genes of the ceRNA network were also demonstrated by dual-luciferase reporter assay.

Results

PWRN2 was found to be associated with oocyte nuclear maturation in patients with PCOS in contrast to that in normal patients. Based on the microarray data, 176 lncRNAs (118 up-regulated and 58 down-regulated) and 131 mRNAs (84 up-regulated and 47 down-regulated) were identified to be regulated by PWRN2. A PWRN2-miR-92b-3p- TMEM120B ceRNA network was constructed based on results of analysis of the combined three microarray datasets (lncRNA+mRNA microarray in KGN/shPWRN2 in this study, miRNAs microarray and lncRNA+mRNA microarray in PCOS cumulus cells reported in previous studies). The coexpression characteristics of the genes ( PWRN2, miR-92b-3p and TMEM120B) were detected in the cumulus cells of cumulus-oocyte complexes at different nuclear maturity stages in PCOS. These results are in accordance with the ceRNA hypothesis. Moreover, luciferase activity assay revealed that miR-92b-3p directly binds to PWRN2 and targets TMEM120B.

Conclusions

PWNR2 plays important roles in oocyte nuclear maturation in PCOS by functioning as a ceRNA to reduce the availability of miR-92b-3p for TMEM120B target binding during oocyte maturation in PCOS. Our findings would provide new information and clarify abnormal oocyte development in PCOS.

Electronic supplementary material

The online version of this article (10.1186/s12958-018-0392-4) contains supplementary material, which is available to authorized users.

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Author and article information

Contributors

Xin Huang:

ORCID: http://orcid.org/0000-0003-3665-8122

86-15905355585 , huangxin92129@163.com

Jiaping Pan: ritapan77@51mch.com

Bi Wu: biowubi@163.com

Xiaoming Teng: 86-15905355585 , tengxiaoming@hotmail.com

Journal

Journal ID (nlm-ta): Reprod Biol Endocrinol

Journal ID (iso-abbrev): Reprod. Biol. Endocrinol

Title: Reproductive Biology and Endocrinology : RB&E

Publisher: BioMed Central (London )

ISSN (Electronic): 1477-7827

Publication date (Electronic): 3 August 2018

Publication date PMC-release: 3 August 2018

Publication date Collection: 2018

Volume: 16

Electronic Location Identifier: 73

Affiliations

ISNI 0000000123704535, GRID grid.24516.34, Department of Assisted Reproductive Medicine, Shanghai First Maternity and Infant Hospital, , Tongji University School of Medicine, ; 2699 Gaoke Road West, Shanghai, 200001 People’s Republic of China

Author information

Xin Huang http://orcid.org/0000-0003-3665-8122

Article

Publisher ID: 392

DOI: 10.1186/s12958-018-0392-4

PMC ID: 6091030

PubMed ID: 30075721

SO-VID: 536bd7d1-a880-471f-ae02-82f616b5c78f

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 29 March 2018

Date accepted : 25 July 2018

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81401172

Award ID: 81771532

Award Recipient : Xin Huang

Funded by: Special Fund for Clinical Medicine Scientific Research of Chinese Medical Association

Award ID: 16020180634

Award Recipient : Xin Huang

Funded by: Shanghai municipal medical and health discipline construction projects

Award ID: 2017ZZ02015

Award Recipient : Xiaoming Teng

Custom metadata

ScienceOpen disciplines: Human biology

Keywords: cerna,oocyte maturation,polycystic ovary syndrome,pwrn2,mir-92b-3p,tmem120b

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ScienceOpen disciplines: Human biology

Keywords: cerna, oocyte maturation, polycystic ovary syndrome, pwrn2, mir-92b-3p, tmem120b

Construction and analysis of a lncRNA ( PWRN2)-mediated ceRNA network reveal its potential roles in oocyte nuclear maturation of patients with PCOS

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Most cited references 31

Non-coding RNAs: the architects of eukaryotic complexity.

Human β cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes.

Transcribed dark matter: meaning or myth?

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