Open Access

ARTICLE

circACTN4 promotes breast cancer cell cycle progression and oncogenesis via c-MYC induced histone H4 acetylation

KEFAN LIU¹, XIAOSONG WANG¹, XIN YANG¹, BOWEN SHI¹, LEI XING^2,*, JUNXIA CHEN^1,*

1 Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, 400016, China
2 Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China

* Corresponding Authors: LEI XING. Email: ; JUNXIA CHEN. Email:

(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis)

Oncology Research 2025, 33(7), 1709-1722. https://doi.org/10.32604/or.2025.061721

Received 01 December 2024; Accepted 07 March 2025; Issue published 26 June 2025

Abstract

Background: Accumulating studies have shown the important role of circular RNAs (circRNAs) in the oncogenesis and metastasis of various cancers. We previously reported that circACTN4 could bind with FUBP1 to promote tumorigenesis and the development of breast cancer (BC) by increasing the expression of MYC. However, its exact molecular mechanism and biological function have not been fully elucidated. Methods: Here, Circular RNA microarray analysis was conducted in 3 pairs of BC and paracancerous tissues. The expression of circACTN4 in BC cells and tissues was detected via reverse transcription‒quantitative PCR (RT‒qPCR). Cell Counting Kit-8 (CCK-8), 5-ethynyl-2-deoxyuridine (EdU), transwell migration, and invasion assays were performed to further detect the biological functions of circACTN4 in BC cells. Xenograft models were used to investigate the in vivo role of circACTN4. Fluorescence in situ hybridization, Chromatin immunoprecipitation (ChIP)‒qPCR, coimmunoprecipitation, fluorometric, western blot, and rescue experiments were performed to explore the mechanism of circACTN4. Results: Our results revealed that circACTN4 was highly expressed in BC cells and tissues. The upregulated expression of circACTN4 was significantly related to the T stage and TNM stage and poor prognosis of patients with BC. circACTN4 was located primarily in the nucleus of BC cells. Upregulation of circACTN4 significantly increased the proliferation, invasion, and growth of BC cells, whereas the downregulation of circACTN4 exerted the opposite effects and induced G1/S cell cycle arrest. Mechanistically, we showed that circACTN4 could upregulate the expression of MYC and that MYC might interact with TIP60 histone acetyltransferase to increase the recruitment of TIP60 to MYC target genes and histone H4 acetylation (AcH4), thus promoting the progression of the breast cancer cell cycle and tumorigenesis. Conclusion: Taken together, our findings reveal for the first time a new mechanism by which circACTN4 could promote oncogenesis and the development of BC by increasing the AcH4 of MYC target genes via TIP60. Therefore, circACTN4 could be a novel target for BC diagnosis and remedy.

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