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

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.

MicroRNAs and Gene Regulatory Networks Related to Cleft Lip and Palate

“…In cultured human and mouse lip mesenchymal cells, miR-27b inhibits cell proliferation through gene suppression of PAX9 and RARA ; miR-133b inhibits cell proliferation through gene suppression of FGFR1 , PAX7 , and SUMO1 ; and miR-205 inhibits cell proliferation through gene suppression of PAX9 and RARA [ 55 ]. miR-27b-3p has been reported to be a tumor suppressor, inhibiting cell proliferation and migration through target gene expression in several cancer cells: TAB3 in hepatocellular carcinoma [ 56 ], MLL4 in glioblastoma stem cells [ 57 ], TMED5 in gastric cancer cells [ 58 ], and CTNNB1 in ovarian endometrial cells [ 59 ]. Overexpression of miR-133b suppresses cell proliferation viability and migration in various cancer cells: prostatic carcinoma cells through ZNF587 [ 60 ] or SDCCAG3 expression [ 61 ], cervical cancer cells through ARFGEF1 expression [ 62 ], and lung adenocarcinoma through CDCA8 expression [ 63 ].…”

A comprehensive overview of exosome lncRNAs: emerging biomarkers and potential therapeutics in endometriosis

“…This could enhance the repressive effect of miR-10b on its target gene SDC1 , which would reduce cell-cell and cell-matrix adhesion, facilitating the invasion of ectopic endometrial glandular epithelial cells ( 80 ). The growth of endometriosis and the interactions between miRNAs and lncRNAs are tightly connected, and endometriosis proliferation, invasion, and metastasis are all significantly impacted by these factors ( 81 , 82 ).…”

Inhibition of ox‐LDL‐induced endothelial cell injury by LINC02381 knockdown through the microRNA‐491‐5p/transcription factor 7 axis

“…In addition, LINC02381 has been suggested to act as a miRNA sponge for various miRNAs, including miR-27b-3p, miR-1271-5p, and miR-21. [24][25][26] However, the role of LINC02381 and its relationship with miR-491-5p in the pathophysiology of AS remain unclear. In this study, we investigated whether LINC02381 exerts a role in ox-LDL-induced endothelial injury by modulating miR-491-5p expression using in vitro experiments with HUVECs.…”

“…LINC02381 has been studied in several types of cancers and found to be involved in inflammatory diseases. In addition, LINC02381 has been suggested to act as a miRNA sponge for various miRNAs, including miR‐27b‐3p, miR‐1271‐5p, and miR‐21 24–26 . However, the role of LINC02381 and its relationship with miR‐491‐5p in the pathophysiology of AS remain unclear.…”