Adaptive drug resistance mechanisms driven by non-coding RNA-protein interaction networks in hepatocellular carcinoma

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Hepatocellular carcinoma (HCC) presents significant mortality due to tumor heterogeneity and treatment resistance.
• Noncoding RNAs (ncRNAs) and RNA-binding proteins (RBPs) play critical roles in regulating complex cellular processes.
• Understanding the interplay between ncRNAs and RBPs is crucial for deciphering HCC progression and resistance mechanisms.

Purpose of the Study:

• To review recent advances in understanding how ncRNAs and RBPs regulate key pathways in HCC.
• To highlight novel mechanisms, including RNA modifications and phase separation, governing ncRNA-RBP interactions.
• To explore the therapeutic potential of targeting ncRNA-RBP axes for precision oncology in HCC.

Main Methods:

• Literature review of recent mechanistic studies on ncRNAs, RBPs, and HCC.
• Analysis of emerging principles in ncRNA-RBP interaction specificity.
• Discussion of multi-omics and spatial profiling technologies for identifying resistance-associated networks.

Main Results:

• ncRNAs, including lncRNAs and circRNAs, collaborate with RBPs to control ferroptosis, autophagy, lipid metabolism, immune evasion, and transcriptional programs in HCC.
• RNA chemical modifications, structural elements, and liquid-liquid phase separation are key determinants of ncRNA-RBP interaction specificity.
• Multi-omics and spatial profiling reveal critical ncRNA-protein networks associated with therapeutic resistance in HCC.

Conclusions:

• Targeting ncRNA-RBP interactions presents actionable therapeutic opportunities for HCC.
• Understanding these regulatory circuits can guide biomarker development and personalized treatment strategies.
• This framework supports the advancement of precision oncology for hepatocellular carcinoma.