RNA splicing: a dual-edged sword for hepatocellular carcinoma

Area of Science:

• Molecular Biology
• Cancer Biology
• Genetics

Background:

• Alternative RNA splicing (ARS) generates transcriptome and proteome diversity, crucial for cellular function.
• Aberrant ARS is implicated in various diseases, notably cancer, where it influences tumor progression and patient survival.
• Hepatocellular carcinoma (HCC), a major liver cancer, exhibits numerous ARS events affecting key genes.

Purpose of the Study:

• To discuss RNA splicing events and aberrations in hepatocellular carcinoma (HCC).
• To explore the role of antisense oligonucleotides (ASOs) in modulating RNA splicing for HCC therapy.
• To highlight the therapeutic potential of targeting ARS in liver cancer.

Main Methods:

• Review of scientific literature on RNA splicing, HCC, and therapeutic strategies.
• Analysis of alternative splicing events, including intron retention and exon skipping in HCC.
• Discussion of spliceosome and non-spliceosome gene involvement in cancer.

Main Results:

• Dysregulated ARS significantly impacts HCC tumor progression, invasiveness, and patient outcomes.
• Specific ARS events in HCC can lead to anti-apoptotic isoforms, conferring chemoresistance.
• Targeting pro-apoptotic splicing variants can enhance chemotherapy efficacy in HCC.

Conclusions:

• Altering RNA splicing presents a promising therapeutic avenue for HCC.
• Antisense oligonucleotides (ASOs) show potential for modulating aberrant splicing in liver cancer.
• Targeting ARS aberrations could overcome chemotherapy resistance in HCC.