2. Academic Validation
  3. RUNX1-IT1 favors breast cancer carcinogenesis through regulation of IGF2BP1/GPX4 axis

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

  • Discov Oncol. 2023 Apr 10;14(1):42. doi: 10.1007/s12672-023-00652-z.
Shengting Wang 1,  Yufang Wang 2,  Qian Li 2,  Kaixuan Zeng 3,  Xiaoming Li 2,  Xinghua Feng 2
Affiliations

Affiliations

  • 1 Clinical Medical Center, Xi'an Peihua University, 888 Changning Street, Xi'an, 710125, Shaanxi, China. stwang@peihua.edu.cn.
  • 2 Clinical Medical Center, Xi'an Peihua University, 888 Changning Street, Xi'an, 710125, Shaanxi, China.
  • 3 School of Medicine, Xi'an Jiaotong University, Xi'an, 710000, China.
PMID: 37036576 DOI: 10.1007/s12672-023-00652-z
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.

Keywords

Breast cancer; Ferroptosis; Long non-coding RNA; m6A reader; mRNA stability.

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