Noncanonical formation of SNX5 gene-derived circular RNA regulates cancer growth.

Aug 19, 2024

Experts: Yi-Tung Chen,Hui-Ju Tsai,Chia-Hua Kan,Chung-Pei Ma,Hui-Wen Chen,Ian Yi-Feng Chang,Hsuan Liu,Chih-Ching Wu,Wei-Yun Chu,Ya-Chun Wu,Kai-Ping Chang,Jau-Song Yu,Bertrand Chin-Ming Tan

Oral squamous cell carcinoma (OSCC) is a prevalent cancer worldwide, exhibiting unique regional prevalence. Despite advancements in diagnostics and therapy, the 5-year survival rate for patients has seen limited improvement. A deeper understanding of OSCC pathogenesis, especially its molecular underpinnings, is essential for improving detection, prevention, and treatment. In this context, noncoding RNAs, such as circular RNAs (circRNAs), have gained recognition as crucial regulators and potential biomarkers in OSCC progression. Our study highlights the discovery of previously uncharacterized circRNAs, including a SNX5 gene-derived circRNA, circSNX5, through deep sequencing of OSCC patient tissue transcriptomes. We established circSNX5’s tumor-specific expression and its strong correlation with patient survival using structure-specific and quantitative PCR analyses. In vitro and in vivo experiments underscored circSNX5 RNA’s regulatory role in cancer growth and metastasis. Further, our omics profiling and functional assays revealed that ADAM10 is a critical effector in circSNX5-mediated cancer progression, with circSNX5 maintaining ADAM10 expression by sponging miR-323. This novel circRNA-miRNA-mRNA regulatory axis significantly contributes to oral cancer progression and malignancy. Moreover, we discovered that circSNX5 RNA is produced via noncanonical sequential back-splicing of pre-mRNA, a process negatively regulated by the RNA-binding protein STAU1. This finding adds a new dimension to our understanding of exonic circRNA biogenesis in the eukaryotic transcriptome. Collectively, our findings offer a detailed mechanistic dissection and functional interpretation of a novel circRNA, shedding light on the role of the noncoding transcriptome in cancer biology and potentially paving the way for innovative therapeutic strategies.
© 2024. The Author(s).

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ABOUT THE EXPERTS

Yi-Tung Chen,Hui-Ju Tsai,Chia-Hua Kan,Chung-Pei Ma,Hui-Wen Chen,Ian Yi-Feng Chang,Hsuan Liu,Chih-Ching Wu,Wei-Yun Chu,Ya-Chun Wu,Kai-Ping Chang,Jau-Song Yu,Bertrand Chin-Ming Tan

Yi-Tung Chen

Molecular Medicine Research Center, Chang Gung University, Taoyuan, 333, Taiwan.

Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Hui-Ju Tsai

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Chia-Hua Kan

Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Chung-Pei Ma

Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Hui-Wen Chen

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Ian Yi-Feng Chang

Molecular Medicine Research Center, Chang Gung University, Taoyuan, 333, Taiwan.

Department of Neurosurgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.

Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.

Hsuan Liu

Molecular Medicine Research Center, Chang Gung University, Taoyuan, 333, Taiwan.

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Division of Colon and Rectal Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.

Chih-Ching Wu

Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Wei-Yun Chu

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Ya-Chun Wu

Asia American International Academy, New Taipei City, Taiwan.

Kai-Ping Chang

Molecular Medicine Research Center, Chang Gung University, Taoyuan, 333, Taiwan.

Department of Otolaryngology-Head & Neck Surgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan.

Jau-Song Yu

Molecular Medicine Research Center, Chang Gung University, Taoyuan, 333, Taiwan.

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan.

Bertrand Chin-Ming Tan

Department of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan. btan@mail.cgu.edu.tw.

Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, 333, Taiwan. btan@mail.cgu.edu.tw.

Department of Neurosurgery, Lin-Kou Medical Center, Chang Gung Memorial Hospital, Taoyuan, 333, Taiwan. btan@mail.cgu.edu.tw.

Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, 333, Taiwan. btan@mail.cgu.edu.tw.