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

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 of CRC. Consequently, the urgency to...

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Main Authors: Chu Hao, Yunju Pu, Jiunian Li, Zhi Zhong, Zhaohui Huang, Xue Wang
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Journal of Cancer Research and Clinical Oncology
Subjects:
Online Access:https://doi.org/10.1007/s00432-025-06092-2
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author Chu Hao
Yunju Pu
Jiunian Li
Zhi Zhong
Zhaohui Huang
Xue Wang
author_facet Chu Hao
Yunju Pu
Jiunian Li
Zhi Zhong
Zhaohui Huang
Xue Wang
author_sort Chu Hao
collection DOAJ
description 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 of CRC. 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 of CRC. 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 of circWDR78 as a potential regulatory axis of miR-653-3p/RGS4 in CRC progression.
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spelling doaj-art-e6f80b3a307640daafd0fd4defbe6a592025-02-09T12:10:39ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-02-01151211210.1007/s00432-025-06092-2CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axisChu Hao0Yunju Pu1Jiunian Li2Zhi Zhong3Zhaohui Huang4Xue Wang5Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityLaboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan UniversityAbstract 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 of CRC. 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 of CRC. 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 of circWDR78 as a potential regulatory axis of miR-653-3p/RGS4 in CRC progression.https://doi.org/10.1007/s00432-025-06092-2Colorectal cancercircWDR78miR-653-3pRGS4
spellingShingle Chu Hao
Yunju Pu
Jiunian Li
Zhi Zhong
Zhaohui Huang
Xue Wang
CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
Journal of Cancer Research and Clinical Oncology
Colorectal cancer
circWDR78
miR-653-3p
RGS4
title CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
title_full CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
title_fullStr CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
title_full_unstemmed CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
title_short CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
title_sort circwdr78 inhibits the development of colorectal cancer by regulating the mir 653 3p rgs4 axis
topic Colorectal cancer
circWDR78
miR-653-3p
RGS4
url https://doi.org/10.1007/s00432-025-06092-2
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