Long non-coding RNA DHRS4 antisense RNA 1 inhibits ectopic endometrial cell proliferation, migration, and invasion in endometriosis by regulating microRNA-139-5p expression.

Abstract

Endometriosis is an estrogen-dependent chronic gynecological syndrome. Recent studies have shown that long non-coding RNAs participate in the pathogenesis and development of endometriosis. This study aimed to explore the mechanisms of DHRS4 antisense RNA 1 (DHRS4-AS1) in endometriosis. Dual-luciferase reporter assays were conducted to determine the relationship between DHRS4-AS1, microRNA (miR)-139-5p, and arrestin domain-containing 3 (ARRDC3). Furthermore, the expression of DHRS4-AS1 and miR-139-5p in ectopic endometrial stromal cells (EC-ESCs) and endometriosis tissues was examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), flow cytometry, and Transwell assays were performed to evaluate the proliferation, apoptosis, and migration and invasion of EC-ESCs, respectively. Western blotting and RT-qPCR were further utilized to determine cleaved-Caspase 3, Caspase 3, and matrix metalloproteinase 9 (MMP-9) expression levels. Compared with the EN group, DHRS4-AS1 levels were lower and miR-139-5p levels were higher in EC-ESCs and tissues obtained from patients with endometriosis. Functional assays validated that DHRS4-AS1 targets miR-139-5p, with ARRDC3 being a downstream target of miR-139-5p. Rescue experiments demonstrated that DHRS4-AS1 inhibited EC-ESC proliferation, migration, and invasion, but promoted apoptosis, by targeting miR-139-5p in endometriosis. cleaved-Caspase3 expression level and the cleaved-Caspase 3/Caspase 3 ratio increased, while the expression levels of MMP-9 decreased, after transfection with DHRS4-AS1 overexpression plasmids; however, the effects induced by DHRS4-AS1 overexpression could be partially reversed by co-transfection with the miR-139-5p mimic. The current study demonstrates that the DHRS4-AS1/miR-139-5p/ARRDC3 axis participates in the regulation of EC-ESC function.

• Authors: Xuan Cui, Shisan Zhou, Yongtao Lin
• Journal: Bioengineered (Bioengineered) Vol. 13 Issue 4 Pg. 9792-9804 (04 2022) ISSN: 2165-5987 [Electronic] United States
• PMID: 35414313 (Publication Type: Journal Article)

Chemical References

• MIRN139 microRNA, human
• MicroRNAs
• RNA, Antisense
• RNA, Long Noncoding
• Oxidoreductases
• DHRS4 protein, human
• Caspase 3
• Matrix Metalloproteinase 9

Topics

• Caspase 3
• Cell Line, Tumor
• Cell Movement (genetics)
• Cell Proliferation (genetics)
• Endometriosis (genetics, metabolism)
• Female
• Humans
• Matrix Metalloproteinase 9 (genetics)
• MicroRNAs (genetics, metabolism)
• Oxidoreductases
• RNA, Antisense (genetics)
• RNA, Long Noncoding (genetics, metabolism)