CircRNA-encoded RIPK1-98 protein drives lung adenocarcinoma progression

Area of Science:

• Molecular Biology
• Genomics
• Oncology

Background:

• Uncharacterized biological matter, including genetic elements and proteins, presents knowledge gaps.
• Circular RNAs (circRNAs) are increasingly recognized for their complex roles beyond microRNA sponging.
• Understanding novel protein products from circRNAs is crucial for advancing cancer research.

Purpose of the Study:

• To identify and characterize novel protein products encoded by circRNAs in human lung adenocarcinoma (LUAD) tissues.
• To investigate the functional roles of these circRNA-encoded proteins in LUAD progression.
• To explore the potential of these proteins as biomarkers and therapeutic targets in LUAD.

Main Methods:

• Integrated multi-omics approaches were employed for comprehensive analysis.
• Functional and translational analyses were conducted using cellular and animal models.
• Specific focus on the transcription of precursor mRNA by RNA polymerase II subunit A (RPB1) for protein biogenesis.

Main Results:

• Previously unrecognized protein products encoded by circRNAs were identified in human LUAD specimens.
• The protein RIPK1-98, encoded by circRIPK1, was found to be functionally distinct from its parental RIPK1.
• RIPK1-98 was shown to modulate cyclin-dependent kinase 2 (CDK2)-dependent cell-cycle regulation, promoting tumor proliferation.

Conclusions:

• RIPK1-98, a novel circRNA-encoded protein, plays a significant role in LUAD cell-cycle progression.
• RIPK1-98 serves as a potential biomarker for cell-cycle progression in LUAD.
• RIPK1-98 represents a promising therapeutic target to overcome resistance to treatments like osimertinib.