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Discover Oncology
Published in: Discover Oncology 1/2023

Open Access 01-12-2023 | Breast Cancer | Research

RUNX1-IT1 favors breast cancer carcinogenesis through regulation of IGF2BP1/GPX4 axis

Authors: Shengting Wang, Yufang Wang, Qian Li, Kaixuan Zeng, Xiaoming Li, Xinghua Feng

Published in: Discover Oncology | Issue 1/2023

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Abstract

Breast cancer is the most common malignancy among women and the leading cause of cancer deaths, with complicated pathogenesis that is largely unknown. In this study, we identified a novel long non-coding RNA (lncRNA) as a critical driver of breast cancer tumorigenesis. RUNX1 intronic transcript 1 (RUNX1-IT1) was notably overexpressed in human breast cancer tissues, and knockdown of RUNX1-IT1 inhibited breast cancer cell viability and invasion, as well as tumor growth in orthotopic transplantation model. Further, RUNX1-IT1 repressed ferroptosis, a novel iron-dependent form of regulated cell death, via increasing glutathione peroxidase 4 (GPX4) expression. Specifically, RUNX1-IT1 directly bound to N6-methyladenosine m6A reader IGF2BP1 and promoted the formation of (insulin like growth factor 2 mRNA binding protein 1) IGF2BP1 liquid-liquid phase separation (LLPS) biomolecular condensates, resulting in more IGF2BP1 occupation on GPX4 mRNA, increasing GPX4 mRNA stability. Moreover, high RUNX1-IT1 was linked to poor prognosis, and a strong positive correlation between RUNX1-IT1 and GPX4 was observed in clinical breast cancer tissues. Taken together, our data reveal that RUNX1-IT1 promotes breast cancer carcinogenesis through blocking ferroptosis via elevating GPX4, targeting of the previously unappreciated regulatory axis of RUNX1-IT1/IGF2BP1/GPX4 may be a promising treatment for patient with breast cancer.
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Metadata
Title
RUNX1-IT1 favors breast cancer carcinogenesis through regulation of IGF2BP1/GPX4 axis
Authors
Shengting Wang
Yufang Wang
Qian Li
Kaixuan Zeng
Xiaoming Li
Xinghua Feng
Publication date
01-12-2023
Publisher
Springer US
Published in
Discover Oncology / Issue 1/2023
Print ISSN: 1868-8497
Electronic ISSN: 2730-6011
DOI
https://doi.org/10.1007/s12672-023-00652-z

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