Single-cell transcriptome analysis reveals regulatory programs of prognosis-associated RNA binding proteins during...

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Hepatocellular carcinoma (HCC) is an aggressive liver cancer with poorly understood RNA-binding protein (RBP) expression heterogeneity.
• Investigating RBP heterogeneity at the single-cell level is crucial for understanding HCC progression and identifying therapeutic targets.

Purpose of the Study:

• To investigate single-cell-level RBP heterogeneity in HCC.
• To explore the regulatory roles of RBPs in HCC progression.
• To assess the therapeutic potential of RBPs in HCC.

Main Methods:

• Univariate Cox analysis and NMF algorithm were used to screen prognostic RBPs and stratify tumor clusters.
• Single-cell RNA sequencing was employed to analyze RBP heterogeneity in malignant and myeloid-derived cells.
• In vitro assays (CCK-8, EdU, Transwell) and SpliceSeq analysis validated the role of HDGF.

Main Results:

• RBP expression significantly correlated with HCC grades, with prognostic RBPs enriched in ribosome biogenesis pathways.
• Single-cell analysis revealed distinct RBP patterns in primary vs. recurrent HCCs, identifying YRDC and HDGF as key regulators.
• HDGF promoted HCC cell proliferation, migration, and invasion, and was implicated in survival-associated alternative splicing events.

Conclusions:

• RBPs exhibit single-cell heterogeneity and are linked to HCC progression pathways.
• HDGF is identified as a candidate oncogenic RBP based on in vitro and splicing data.
• RBPs, including HDGF, represent promising targets for future HCC mechanistic and therapeutic research.