Circ_FURIN knockdown assuages Testosterone-induced human ovarian granulosa-like tumor cell disorders by sponging miR-423-5p to reduce MTM1 expression in polycystic ovary syndrome

© 2022. The Author(s)..

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism.

METHODS: PCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays.

RESULTS: Circ_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p.

CONCLUSION: Circ_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:20

Enthalten in:

Reproductive biology and endocrinology : RB&E - 20(2022), 1 vom: 17. Feb., Seite 32

Sprache:

Englisch

Beteiligte Personen:

Xu, Xia [VerfasserIn]
Guan, Rui [VerfasserIn]
Gong, Ke [VerfasserIn]
Xie, Huaibing [VerfasserIn]
Shi, Lei [VerfasserIn]

Links:

Volltext

Themen:

3XMK78S47O
Circ_furin
EC 3.1.3.48
EC 3.4.21.75
FURIN protein, human
Furin
Journal Article
MIRN423 microRNA, human
MTM1
MiR-423-5p
MicroRNAs
Myotubularin
PCOS
Protein Tyrosine Phosphatases, Non-Receptor
RNA, Circular
TTR
Testosterone

Anmerkungen:

Date Completed 23.03.2022

Date Revised 23.03.2022

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12958-022-00891-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM337089639