Long Intergenic Non-Protein Coding RNA 02381 Promotes the Proliferation and Invasion of Ovarian Endometrial Stromal Cells through the miR-27b-3p/CTNNB1 Axis.

Jingwen Zhu,Xiaoqing Wang,Peili Wu,Cheng Zeng,Qing Xue,Yingfang Zhou,Ye Lu

doi:10.3390/genes13030433

Jingwen Zhu, Xiaoqing Wang + Show 5 more

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https://doi.org/10.3390/genes13030433

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Journal: Genes	Publication Date: Feb 26, 2022
Citations: 4	License type: CC BY 4.0

Affiliation: Peking University First Hospital, Peking University

Abstract

Purpose: Catenin Beta 1 (CTNNB1) is a key regulator of cell proliferation and invasion in endometriosis; however, its upstream factor is not clear. Long noncoding RNAs may participate in endometriosis. The aim of this study was to investigate the mechanism of interaction between LINC02381 and CTNNB1 in endometriosis. Method: Screening and validation of RNAs were completed by whole transcriptional sequencing and qRT-PCR. The subcellular localization of LINC02381 was determined by RNA in situ hybridization and nucleo-cytoplasmic separation. Plasmids were transfected for functional experiments. Luciferase assay was used to verify the binding relationship. Results: The expression of LINC02381 and CTNNB1 was significantly increased in ovarian ectopic endometrial tissues (OSAs) and ectopic endometrial stromal cells (ESCs). When LINC02381 was downregulated in ESCs, the expression of CTNNB1, metallopeptidase 9 (MMP9) and cyclinD1, as well as ESCs invasion and proliferation, decreased. LINC02381 was mainly present in the cytoplasm of ESCs, indicating that it may act as a competitive endogenous RNA. Bioinformatic analysis revealed that microRNA-27b-3p (miR-27b-3p) is a downstream target of LINC02381. miR-27b-3p decreased in OSAs and ESCs. Moreover, when miR-27b-3p was upregulated in ESCs, the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability of ESCs, were reduced. Additionally, rescue experiments demonstrated that the expression of CTNNB1, MMP9 and cyclinD1, as well as the invasion and proliferation ability, were significantly increased in the group transfected with both sh-LINC02381 and a miR-27b-3p inhibitor. Conclusion: LINC02381 upregulated CTNNB1 by adsorbing miR-27b-3p, causing increased proliferation and invasion of ESCs.

Highlights

Publisher’s Note: MDPI stays neutralEndometriosis is a benign gynecological disorder that affects 10% of reproductive-aged women
matrix metalloproteinase (MMP) are capable of facilitating cell invasion in endometriosis by degrading the primary structure of the extracellular matrix and basement membrane [7]
Fluorescence in situ hybridization (RNA fluorescent in situ hybridization (FISH)) and nuclear-cytoplasmic fractionation, we found that LINC02381 mainly existed in the cytoplasm of endometrial stromal cells (ESCs), suggesting that LINC02381 might play an important role as a competitive endogenous RNA (ceRNA)

Summary

Introduction

Endometriosis is a benign gynecological disorder that affects 10% of reproductive-aged women. It is characterized by the outgrowth of endometrial cells from the lining of the uterus outside the uterine cavity [1], with pelvic pain and infertility being its main clinical manifestations [2–4]. Sampson [5] first described endometriosis as being caused by retrograde movement of the endometrium through the fallopian tube, thereby invading and proliferating in tissues outside the uterus. The proliferation and invasion of endometrial stromal cells (ESCs) are regulated by cyclinD1 and matrix metalloproteinase (MMP) 9, which are important markers of endometriosis [6,7]. MMPs are capable of facilitating cell invasion in endometriosis by degrading the primary structure of the extracellular matrix and basement membrane [7]. CyclinD1, which is a cell cycle regulator, is essential for progression through the G1 phase and is a prominent prognostic marker for endometrial with regard to jurisdictional claims in published maps and institutional affiliations

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