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Inhibition of KIF20A by transcription factor IRF6 affects the progression of renal clear cell carcinoma
Xinwei Ma1,2, Xiaoqi Wang3, Qian Dong2
1Department of Radiology, The Second Affiliated Hospital of Soochow University, No.1055 Sanxiang Road, Suzhou, 215004, Jiangsu, China.
Background:
Renal clear cell carcinoma (ccRCC) is one of the most common malignant tumors, whose incidence is increasing year by year. IRF6 plays an important role in the occurrence of tumors, although there is yet no report on its expression in ccRCC.
Methods:
The expression of IRF6 and KIF20A in ccRCC was predicted by GEPIA and HAP databases. In addition, GEPIA database predicted the relationship between IRF6 and KIF20A expressions and the pathological staging, overall survival, and disease-free survival of ccRCC. The possible binding sites of IRF6 and KIF20A promoters were predicted by JASPAR database and verified by luciferase and ChIP assays. The specific effects of IRF6 on ccRCC cell proliferation, invasion and apoptosis were subsequently examined at both cellular level and animal level.
Results:
The database predicted down-regulated IRF6 expression in renal carcinoma tissues and its correlation with poor prognosis. IRF6 overexpression inhibited cRCC cell proliferation, invasion and migration. In addition, up-regulated KIF20A expression in renal carcinoma tissues and its association with prognosis were also predicted. Interference with KIF20A inhibited the proliferation, invasion, and migration of ccRCC cells. Finally, we confirmed that KIF20A is a functional target of IRF6 and can partially reverse the effects of IRF6 on the proliferation, invasion and migration of ccRCC cells.
Conclusion:
Inhibition of KIF20A by transcription factor IRF6 affects cell proliferation, invasion and migration in renal clear cell carcinoma.
Insights
Interferon regulatory factor 6 (IRF6) is downregulated in renal clear cell carcinoma (ccRCC), inhibiting tumor progression. Its target, KIF20A, is upregulated and promotes ccRCC cell proliferation and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Renal clear cell carcinoma (ccRCC) is a prevalent malignancy with increasing incidence.
- The role of Interferon Regulatory Factor 6 (IRF6) in ccRCC remains uncharacterized despite its known involvement in tumorigenesis.
Purpose of the Study:
- To investigate the expression and function of IRF6 in ccRCC.
- To explore the relationship between IRF6, KIF20A, and ccRCC progression.
- To elucidate the underlying molecular mechanisms of IRF6 in ccRCC.
Main Methods:
- Bioinformatic analysis using GEPIA and HAP databases for gene expression and survival correlation.
- Promoter analysis using JASPAR database.
- Experimental validation including luciferase and ChIP assays.
- In vitro and in vivo studies assessing ccRCC cell proliferation, invasion, and apoptosis.
Main Results:
- IRF6 expression is downregulated in ccRCC tissues and correlates with poor prognosis.
- IRF6 overexpression suppresses ccRCC cell proliferation, invasion, and migration.
- KIF20A expression is upregulated in ccRCC tissues and associated with adverse outcomes.
- KIF20A knockdown inhibits ccRCC cell proliferation, invasion, and migration.
- KIF20A is a functional target of IRF6, partially mediating IRF6's effects on ccRCC cells.
Conclusions:
- IRF6 acts as a tumor suppressor in ccRCC by inhibiting cell proliferation, invasion, and migration.
- KIF20A is a key downstream target of IRF6 in ccRCC.
- The IRF6/KIF20A pathway represents a potential therapeutic target for ccRCC.
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