Hypoxia-responsive circular RNA circAAGAB reduces breast cancer malignancy by activating p38 MAPK and sponging miR-378 h.

Autor: Lee KY; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan., Liu CM; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan., Chen LH; Institute of Fisheries Science, College of Life Science, National Taiwan University, Taipei, Taiwan.; Department of Life Science, College of Life Science, National Taiwan University, Taipei, Taiwan., Lee CY; Master Program for Biomedical Engineering, College of Biomedical Engineering, China Medical University, Taichung, Taiwan., Lu TP; Institute of Epidemiology and Preventive Medicine, Department of Public Health, National Taiwan University, Taipei, Taiwan., Chuang LL; School of Physical Therapy and Graduate Institute of Rehabilitation Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan. lchuang@gap.cgu.edu.tw.; Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. lchuang@gap.cgu.edu.tw., Lai LC; Graduate Institute of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan. llai@ntu.edu.tw.; Bioinformatics and Biostatistics Core, Center of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. llai@ntu.edu.tw.
Jazyk: angličtina
Zdroj: Cancer cell international [Cancer Cell Int] 2023 Mar 10; Vol. 23 (1), pp. 45. Date of Electronic Publication: 2023 Mar 10.
DOI: 10.1186/s12935-023-02891-0
Abstrakt: Background: Breast cancer is a prevalent disease in women, with high prevalence worldwide. The hypoxic microenvironment of solid tumors develops during the progress of carcinogenesis and leads to greater malignancy and treatment resistance. Recently, accumulating evidence indicates that non-coding RNAs, such as circular RNAs (circRNAs), play a pivotal role in altering cellular functions. However, the underlying mechanisms of circRNAs in breast cancer are still unclear. Therefore, the purpose of this study was to investigate the role of a tumor-suppressive circRNA, circAAGAB, in breast cancer by assuming down-regulation of circAAGAB under hypoxia and the properties of a tumor suppressor.
Methods: Firstly, circAAGAB was identified from expression profiling by next generation sequencing. Next, the stability of circAAGAB increased by interacting with the RNA binding protein FUS. Moreover, cellular and nuclear fractionation showed that most circAAGAB resided in the cytoplasm and that it up-regulated KIAA1522, NKX3-1, and JADE3 by sponging miR-378 h. Lastly, the functions of circAAGAB were explored by identifying its down-stream genes using Affymetrix microarrays and validated by in vitro assays.
Results: The results showed that circAAGAB reduced cell colony formation, cell migration, and signaling through p38 MAPK pathway, as well as increased radiosensitivity.
Conclusion: These findings suggest that the oxygen-responsive circAAGAB acts as a tumor suppressor in breast cancer, and may contribute to the development of a more specific therapeutic regimen for breast cancer.
(© 2023. The Author(s).)
Databáze: MEDLINE
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