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CircWDR78 inhibits the development of colorectal cancer by regulating the miR-653-3p/RGS4 axis
Chu Hao1, Yunju Pu1, Jiunian Li1
1Laboratory of Cancer Epigenetics, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, 214122, China.
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.
Insights
Circular RNA circWDR78 inhibits colorectal cancer (CRC) progression by downregulating miR-653-3p and its target RGS4. Lower circWDR78 expression correlates with CRC advancement, suggesting its potential as a diagnostic and therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- RNA Biology
Background:
- Colorectal cancer (CRC) presents a significant global health challenge due to increasing mortality rates.
- Low diagnostic accuracy, poor prognosis, and high recurrence contribute to CRC's high mortality.
- Circular RNAs (circRNAs), noncoding RNA molecules with a closed-loop structure, are increasingly recognized for their role in tumor progression.
Purpose of the Study:
- To investigate the role of circWDR78 in colorectal cancer (CRC).
- To explore the molecular mechanisms underlying circWDR78's function in CRC.
- To identify potential diagnostic and therapeutic targets for CRC intervention.
Main Methods:
- Verification of circWDR78's circular structure using Actinomycin D and RNA digestion experiments.
- In vitro functional assays to evaluate proliferation and motility.
- RNA-sequencing to identify regulated pathways and genes.
- Luciferase and qRT-PCR assays to confirm the interaction between circWDR78, miR-653-3p, and RGS4.
Main Results:
- circWDR78 expression is significantly lower in colorectal cancer tissues.
- Downregulation of circWDR78 correlates with increased proliferation, colony formation, and cell motility.
- circWDR78 acts as a molecular sponge for miR-653-3p.
- RGS4 is identified as a novel downstream target of miR-653-3p.
Conclusions:
- circWDR78 functions as a tumor suppressor in colorectal cancer.
- The circWDR78/miR-653-3p/RGS4 axis represents a novel regulatory pathway in CRC progression.
- circWDR78 holds potential as a biomarker and therapeutic target for colorectal cancer.
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