CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis

Sep 23, 2026

Uploaded by Eliana

The study investigates how circular RNA circWDR78 affects colorectal cancer (CRC) progression through the miR-653-3p/RGS4 regulatory axis. CRC remains a major health threat due to limited diagnostic accuracy, poor prognosis, and high recurrence. Using experiments to confirm circWDR78’s circular structure, evaluate proliferation and motility, and analyze downstream pathways with RNA-seq, the work shows circWDR78 functions as a miR-653-3p sponge, targeting RGS4. The results suggest reduced circWDR78 expression suppresses tumor phenotypes, supporting its role in CRC development.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages12

Reading Time30 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusion

Introduction

Circular RNAs in cancer

circWDR78 in CRC

Methods

Cell line and cell culture

Reverse splicing junction of circWDR78

qRT–PCR

Journal of Cancer Research and Clinical Oncology (2025) 151:66 [https://doi.org/10.1007/s00432-025-06092-2](https://doi.org/10.1007/s00432-025-06092-2) RESEARCH CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis Chu Hao1 · Yunju Pu1 · Jiunian Li1 · Zhi Zhong1 · Zhaohui Huang1,2 · Xue Wang1,2 Received: 13 December 2024 / Accepted: 12 January 2025 / Published online: 6 February 2025 © The Author(s) 2025 Abstract Background Colorectal cancer (CRC) stands as one of the most serious threats to human health, with its mortality rate increase during the past years. Low diagnostic accuracy, poor prognosis, and high recurrence rates attributed to the high mortality rate ofCRC. Consequently, the urgency to identify potential diagnose and biological targets for intervention in this disease. Among the various molecular factor associated with this disease, circular RNAs (circRNAs) have been a hot topic. These noncoding RNA molecules, characterized by their unique closed loop structure, displayed close associations with the progression of tumors. Methods Actinomycin D experiment and RNA digestion experiment were used to verify the circular structure characteristics of circWDR78 . Proliferation and motility ability of circWDR78 was evaluated by in vitro functional experiment. We also used RNA-seq technology to explore the signal pathways and genes it might regulate. Finally, the luciferase assay and qRT-PCR experiment proved that circWDR78 could sponge miR-653-3p, and confirmed that RGS4 is the downstream target of miR-653-3p. Results This study demonstrated that circWDR78 is lower expression in colorectal cancer tissues, revealing its capacity to inhibit proliferation, colony forming ability and cell motility. These findings hint at a potential correlation between its downregulation and the progression ofCRC. Mechanistically, we found that circWDR78 could sponge miR-653-3p and identified RGS4 as a novel target of miR-653-3p. Conclusion This discovery highlights the significance ofcircWDR78 as a potential regulatory axis of miR-653-3p/RGS4 in CRC progression. Keywords Colorectal cancer · circWDR78 · miR-653-3p · RGS4 Introduction Colorectal cancer (CRC) is a serious threat to human health. Recent statistics indicate that it has become the third most commonly diagnosed cancer. Although the overall mortality rate for colorectal cancer has decreased in the past years, it still significantly impacts people’s lives. Various risk factors, including gender, age, race, genetics, epigenetics, and the environment contributed to the unpredictability of 􀀍 Xue Wang [mzby_111@163.com](mzby_111@163.com) 1 Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China 2 Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China this disease and trend to be more prevalent among younger individuals (Ye et al. 2023) . Approximately 20% of CRC patients have lymph node metastasis or distant metastasis at diagnosed and another 25% of patients with carcinoma in situ have a risk of potential metastasis, which also leads to the high mortality rate (Siegel et al. 2023; Biller and Schrag 2021). Therefore, it is necessary to identify new biomarkers and therapeutic targets for CRC. CircRNAs differs from traditional linear RNA in that they have a closed-loop structure, making them resistant to RNA exonucleases. As a highly conserved noncoding RNA, circRNAs can influence tumor progression in various ways (Chen 2020; Kristensen et al. 2021; Chen et al. 2020) . The mechanism of circRNAs in regulating cancer related to act as a microRNA sponge. For example, circ_0007379 inhibits CRC progression by regulating the biogenesis of miR-320a in a KSRP-dependent manner (Long et al. 2023) . Additionally, circRNAs can interact with RNA-binding proteins (RBPs) . By interacting with HNRNPC, circ-FIRRE stabilizes GLI2 mRNA and p

FAQs

What is the main regulatory axis proposed in this study?

circWDR78 regulates colorectal cancer progression via the miR-653-3p/RGS4 axis, where circWDR78 acts as a sponge for miR-653-3p and RGS4 functions as the downstream target.

How did the researchers confirm the circular structure of circWDR78?

They used Actinomycin D and RNA digestion experiments to verify the circular structure characteristics of circWDR78.

What functional effects did circWDR78 show in colorectal cancer?

circWDR78 was lower in CRC tissues, and experimental results indicate it can inhibit proliferation, colony-forming ability, and cell motility.

Sep 23, 2026

Uploaded by Eliana