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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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CircOMA1 modulates cabergoline resistance by downregulating ferroptosis in prolactinoma

N Wu1, D Zhu2, J Li1

  • 1Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, China.

Journal of Endocrinological Investigation
|February 28, 2023
PubMed
Abstract

Insights

Circular RNA circOMA1 promotes drug resistance in prolactinomas by inhibiting ferroptosis. This finding suggests circOMA1 as a potential therapeutic target for dopamine agonist-resistant prolactinoma patients.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Prolactinomas are common pituitary tumors, often treated with dopamine agonists (DAs).
  • A subset of patients exhibit resistance to DA pharmacotherapy.
  • Ferroptosis, a regulated cell death pathway, is implicated in tumor drug resistance, but its role in prolactinoma remains unexplored.

Purpose of the Study:

  • To investigate the role of a specific circular RNA (circRNA), circOMA1, in ferroptosis within prolactinoma.
  • To elucidate the underlying molecular mechanisms connecting circOMA1, ferroptosis, and drug resistance in prolactinoma.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) and western blotting were used to assess gene and protein expression.
  • In vitro and in vivo experiments evaluated the biological function of circOMA1.
  • Bioinformatics analysis and luciferase reporter assays identified miR-145-5p as a target of circOMA1 and GCLM as a target of miR-145-5p.

Main Results:

  • circOMA1 was significantly overexpressed in drug-resistant prolactinoma tissues.
  • circOMA1 promoted prolactinoma cell growth both in vitro and in vivo.
  • circOMA1 induced resistance to ferroptosis by upregulating Nrf2, GPX4, and xCT expression.
  • circOMA1 attenuated the ferroptosis induced by cabergoline (CAB) in prolactinoma cells.

Conclusions:

  • circOMA1 contributes to dopamine agonist resistance in prolactinoma by promoting ferroptosis resistance.
  • circOMA1 represents a potential therapeutic target for overcoming drug resistance in prolactinoma patients.
Keywords:
CabergolineCircOMA1Drug resistanceFerroptosisProlactinoma

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