EIF4A3-mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR-381-3p/TNS3 pathway

Sep 21, 2026

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Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to poor prognosis and limited effective therapeutic targets. Circular RNAs (circRNAs) are key regulators in cancer progression. This study uses high-throughput sequencing to show hsa_circ_0001165 is markedly elevated in ESCC tissues and cell lines, with expression positively associated with TNM staging. hsa_circ_0001165 knockdown reduces malignant behavior in vitro and suppresses tumor growth in vivo.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages18

Reading Time45 min

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Introduction

Materials and methods

ESCC tissue specimen and high-throughput sequencing

Cell Biol Toxicol (2024) 40:84 [https://doi.org/10.1007/s10565-024-09927-9](https://doi.org/10.1007/s10565-024-09927-9) EIF4A3‑mediated oncogenic circRNA hsa_circ_0001165 advances esophageal squamous cell carcinoma progression through the miR‑381‑3p/TNS3 pathway Xun Zhang · Yan Bian · Qiuxin Li · Chuting Yu · Ye Gao · Bo Tian · Wenqiang Xia · Wei Wang · Lei Xin · Han Lin · Luowei Wang Received: 25 May 2024 / Accepted: 2 October 2024 / Published online: 9 October 2024 © The Author(s) 2024 Abstract Esophageal squamous cell carcinoma (ESCC) remains a major clinical challenge due to its poor prognosis and the scarcity effective therapeutic targets. Circular RNAs (circRNAs) are crucial in cancer progression. In this study, high-throughput sequencing was employed to profile ESCC tissues, revealing that hsa_circ_0001165 is notably elevated in both ESCC tumor samples and cell lines, with its expression is positively associated with patients’TNM staging. Knockdown of hsa_circ_0001165 resulted in reduced malignant biological behavior of ESCC cells in vitro and also inhibited tumor growth in vivo. Mechanism experimental analysis found that hsa_circ_0001165 expression is positively enhanced by eukaryotic translation initiation factor 4A3 (EIF4A3) . Hsa_circ_0001165 acts as a miRNA | Xun Zhang, Yan Bian and Qiuxin Li these authors contributed equally to this work. | | --- | | Supplementary Information The online version contains supplementary material available at [https://doi](https://doi). org/10.1007/s10565-024-09927-9. | X. Zhang · Y. Bian · Q. Li · C. Yu · Y. Gao · W. Xia · W. Wang · L. Xin (*) · H. Lin (*) · L. Wang (*) Department of Gastroenterology, Changhai Hospital, Naval Medical University, Shanghai 200433, China e-mail: [aip_xin@163.com](aip_xin@163.com) H. Lin [e-mail: babyhan831@aliyun.com](e-mail: babyhan831@aliyun.com) [L. Wang](L. Wang) [e-mail: wangluoweimd@126.com](e-mail: wangluoweimd@126.com) sponge for miR-381-3p, increasing the expression oftensin-3 (TNS3) through a series of related mechanism assays include dual-luciferase reporter gene, RNA Immunoprecipitation and RNA-pulldown. The downregulation in miR-381-3p expression was observed in ESCC tissues, and the cell proliferation, invasion, and migration of ESCC were suppressed. The upregulated expression of hsa_circ_0001165 modulates the miR-381-3p/TNS3 axis and promotes aggressive phenotypes of ESCC. Hsa_circ_0001165 is regarded as a encouraging biomarker and potential therapeutic target for ESCC, presenting innovative options for both diagnostic and treatment approaches. Keywords Esophageal Squamous Cell Carcinoma · Hsa_circ_0001165 · MiR-381-3p · TNS3 X. Zhang · Y. Bian · Q. Li · C. Yu · Y. Gao · B. Tian · W. Xia · W. Wang · L. Xin · H. Lin · L. Wang Digestive Endoscopic Center, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China B. Tian · W. Xia Department of Thoracic Surgery, Changhai Hospital, Naval Medical University, Shanghai 200433, China Introduction A global survey revealed that esophageal cancer ranks as sixth commonly diagnosed cancer type the seventh major reason for cancer-related fatalities (Sung et al. 2021) . The predominant subtype observed in regions such as East Asia and South Africa is esophageal squamous cell carcinoma (ESCC) (Abnet et al. 2018 ; Mazidimoradi et al. 2023) . Although there have been advancements in diagnostic and therapeutic approaches, the survival rate for ESCC patients continues to be disappointing (Huang et al. 2021) . This highlights the necessity for enhanced insights into the molecular mechanisms that contribute to ESCC in order to enhance patient outcomes. Circular RNAs (circRNAs) are noncoding RNAs that are generated via back-splicing. They are distinguished by the lack of a 5’ cap and poly A tail. The inherent stability of circRNAs and their resistance to degradation by nucleases enable their detection in body fluids, underscoring their po

FAQs

What is the main focus of the study on ESCC?

The study investigates how the EIF4A3-mediated circRNA hsa_circ_0001165 drives ESCC progression through the miR-381-3p/TNS3 pathway.

How is hsa_circ_0001165 related to ESCC clinical staging?

hsa_circ_0001165 expression is reported as notably elevated in ESCC samples and cell lines and positively associated with patients’ TNM staging.

What happens to ESCC behavior when hsa_circ_0001165 is knocked down?

Knockdown of hsa_circ_0001165 reduces malignant biological behavior of ESCC cells in vitro and inhibits tumor growth in vivo.

Sep 21, 2026

Uploaded by Rowan