ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Silencing of circRERE(4-5) inhibits ONECUT2-mediated tumorigenesis and metastasis in gastric cancer
Fei Long 1
Hua Xiao 2
Bowen Yu 1
Min Ma 1
Chonglei Zhong 1
Ming Shi 1
Yongxin Ye 1
Qionggui Hu 2
Shiyi Liu 3
Qinpeng Long 4
Kaiyu Zhu 5
1. Department of Gastrointestinal Surgery, Third Xiangya Hospital, Central South University, Changsha, China
2. Hunan Cancer Hospital, Changsha, China
3. Shanghai Jiao Tong University Medical School Affiliated Ruijin Hospital, Shanghai, China
4. First Affiliated Hospital of University of South China, Hengyang, China
5. The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
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Abstract
The leading cause of mortality for gastric cancer (GC) patients is metastasis. Investigating the mechanisms that drive the dissemination of GC could reveal crucial aspects of tumor biology and potentially lead to valuable therapeutic strategies. Circular RNAs (circRNAs), which are extensively expressed in tumors, are involved in a range of biological processes, such as cancer metastasis and cancer immunity. In the present study, the role of circRNAs in the progression and dissemination of GC was investigated. We identified a circRNA, circRERE(4-5) (circBase ID: hsa_circ_0009594), which facilitated GC progression. CircRERE(4-5) was notably elevated in GC tissues and cells, and plasma circRERE(4-5) levels correlated closely with GC size and metastasis. Knockdown of circRERE(4-5) suppressed the growth and movement of GC cells through a pathway involving miR-571 and one cut homeobox 2 (ONECUT2). Moreover, antisense oligonucleotides targeting circRERE(4-5) suppressed the growth and spread of xenograft tumors in mice. Our research uncovers the functional and diagnostic significance of circRERE(4–5) and highlights circRNAs as pivotal factors in GC development and spread.
Summary
Keywords
CircRERE(4-5), circular RNA, gastric cancer, metastasis, Onecut2
Received
15 August 2025
Accepted
18 February 2026
Copyright
© 2026 Long, Xiao, Yu, Ma, Zhong, Shi, Ye, Hu, Liu, Long and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Fei Long
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