Genome-wide analyses identify circAQR, a circular RNA suppressing proliferation but promoting migration and invasion in thyroid cancer

Tianjiao Zhou; Zheng Li; Weijun Huang; Enhui Zhou; Yumeng Jiang; Yueqing Bai; Chen Xu; Wen Lu; Kaiming Su; Chuan Xu; Hongliang Yi

doi:10.1038/s41698-025-00968-9

Genome-wide analyses identify circAQR, a circular RNA suppressing proliferation but promoting migration and invasion in thyroid cancer

NPJ Precis Oncol. 2025 Jun 11;9(1):171. doi: 10.1038/s41698-025-00968-9.

Authors

Tianjiao Zhou^#^{1

2

3}, Zheng Li^#⁴, Weijun Huang^#^{1

2

3}, Enhui Zhou^{1

2

3}, Yumeng Jiang^{1

2

3}, Yueqing Bai⁵, Chen Xu^{1

2

3

6}, Wen Lu^{1

2

3}, Kaiming Su^{1

2

3}, Chuan Xu^{7

8}, Hongliang Yi^{9

10

11}

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, China.
³ Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China.
⁴ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China.
⁵ Department of Pathology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁶ Department of Nursing, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. chuanx@sjtu.edu.cn.
⁸ Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, 200240, China. chuanx@sjtu.edu.cn.
⁹ Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. yihongl@126.com.
¹⁰ Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai, China. yihongl@126.com.
¹¹ Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai, China. yihongl@126.com.

^# Contributed equally.

Abstract

Thyroid cancer frequently metastasizes, even in small lesions, significantly impacting prognosis. Circular RNAs (circRNAs) have emerged as critical regulators of tumor biology; however, their roles in thyroid cancer progression remain poorly understood. Using RNA sequencing data from clinical and GEO-derived samples, we identified 111,971 circRNAs, including 13,399 novel thyroid cancer-specific circRNAs. TNM stage-specific analysis revealed 43 circRNAs positively correlated with tumor size (Rho = 1) and 168 negatively correlated (Rho = -1). Gene Ontology enrichment analysis demonstrated that the target genes of thyroid cancer-specific circRNAs are enriched in cell developmental regulation pathways (NES = 1.74, p < 0.05). Network analysis further suggested that these circRNAs function as competing endogenous RNAs by interacting with tumor-associated microRNAs. Among these, circAQR was significantly associated with tumor size and lymph node metastasis. In vitro experiments revealed that circAQR inhibits proliferation while promoting migration and invasion in thyroid cancer cell lines. These findings highlight the pivotal role of TNM stage-specific circRNAs in thyroid cancer progression, with circAQR showing potential as a biomarker for early metastasis detection and a therapeutic target. The integration of circRNAs into clinical practice could improve early diagnosis and prognostic evaluation, contributing to more effective management of thyroid cancer.

Abstract

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