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ARTICLE

Circ72688 Drives Breast Cancer Invasion and Metastasis via the miR-654-5p/ORAI2 Axis

Haojie Yang1,2,#, Zicong Tan1,2,#, Zihao Liu3,#, Kang Chen1,2, Ning Liufu1,2,*, Fengtao Ji1,2,*
1 Department of Anesthesia, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
2 Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
3 Department of Breast Surgery, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Peking University Cancer Hospital Yunnan, Kunming, China
* Corresponding Author: Ning Liufu. Email: email; Fengtao Ji. Email: email
# These authors contributed equally to this work and share first authorship
(This article belongs to the Special Issue: Novel Biomarkers and Treatment Strategies in Solid Tumor Diagnosis, Progression, and Prognosis (Ⅱ))

Oncology Research https://doi.org/10.32604/or.2026.073081

Received 10 September 2025; Accepted 02 February 2026; Published online 05 March 2026

Abstract

Background: Circular RNAs (circRNAs) play a crucial role in the progression of malignant tumors such as breast cancer. Methods: A circRNA microarray was used to detect key circRNAs in breast cancer. Expression of Circ72688 was verified by quantitative reverse transcription PCR (qRT-PCR) and fluorescence in situ hybridization (FISH) assay. Transwell assay and in vivo assay were conducted to prove the function of Circ72688. Exploring the downstream mechanism, dual-luciferase reporter assay, western blotting, and tissue microarray were performed. Results: We sequenced and identified a circRNA, hsa-circ-0072688, also known as Circ72688. Our research found that Circ72688 enhanced tumor metastasis both in vivo and in vitro. Mechanistically, Circ72688 acted as a molecular sponge for hsa-miR-654-5p, thereby affecting the transcription of ORAI2. The expression levels of Circ72688 and ORAI2 were significantly higher in breast cancer tissues compared to adjacent normal tissues, and a notable positive correlation could be seen between them. Conclusions: In summary, our study demonstrated the critical role of Circ72688 in breast cancer invasion and metastasis, and how Circ72688 partially regulated ORAI2 through hsa-miR-654-5p. Targeting Circ72688 might be a potential therapeutic strategy for breast cancer.

Keywords

Circular RNA; breast cancer; hsa-miR-654-5p; ORAI2; metastasis

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