ZBED6-IGF2-PIK3C3 autophagy axis drives ccRCC progression: A multi-omics integration study

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Autophagy is crucial for clear cell renal cell carcinoma (ccRCC) progression.
• The upstream regulators of autophagy in ccRCC are not fully understood.

Purpose of the Study:

• To identify the regulatory mechanisms controlling autophagy in ccRCC.
• To explore the role of ZBED6 in ccRCC pathogenesis.
• To develop a prognostic signature for ccRCC patients.

Main Methods:

• Integration of bulk, single-cell, and spatial transcriptomics.
• Spatial analysis of ZBED6 and PIK3C3 co-localization.
• Development of a six-gene prognostic signature.
• Functional assays to assess ZBED6's role in ccRCC cell behavior.

Main Results:

• Identified a ZBED6-PIK3C3 axis that activates pro-tumorigenic autophagy via IGF2 repression.
• Confirmed ZBED6 and PIK3C3 co-localization in ccRCC tissues.
• Developed a six-gene signature predicting patient survival and therapy response.
• Demonstrated that ZBED6 enhances ccRCC cell proliferation, migration, and invasion.

Conclusions:

• Elucidated a novel pathway regulating autophagy in ccRCC.
• The ZBED6-PIK3C3 axis is a key driver of ccRCC progression.
• The six-gene signature offers a framework for prognostic assessment and precision therapy in ccRCC.