RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Targeting base excision repair (BER) is a key strategy in cancer therapy.
• RNA-binding motif protein 39 (RBM39) influences cancer-related gene splicing.
• The role of RBM39 in hepatocellular carcinoma (HCC) BER remains unelucidated.

Purpose of the Study:

• To investigate the role of RBM39 in regulating BER in HCC.
• To elucidate the mechanism by which RBM39 affects BER.
• To evaluate the therapeutic potential of targeting RBM39 in HCC.

Main Methods:

• Utilized a BER reporter assay to assess BER efficiency in HCC cells.
• Investigated the effect of RBM39 knockdown and degradation on HCC cell behavior.
• Performed co-immunoprecipitation and mRNA stability assays to determine RBM39-OGG1 interaction.
• Evaluated combination therapy efficacy in vitro and in xenograft mouse models.

Main Results:

• RBM39 knockdown or degradation reduced BER efficiency in HCC cells under oxidative stress.
• RBM39 promoted HCC cell proliferation, migration, invasion, survival, and inhibited apoptosis.
• RBM39 directly interacted with and stabilized 8-oxoguanine-DNA glycosylase 1 (OGG1) mRNA, increasing OGG1 expression.
• Combined RBM39 degradation and oxidative damage demonstrated enhanced anti-tumor effects in vitro and in vivo.

Conclusions:

• RBM39 enhances BER efficiency in HCC by stabilizing OGG1 mRNA.
• RBM39 plays a significant role in HCC progression and survival.
• Combined targeting of RBM39 and oxidative stress presents a potential novel therapeutic strategy for HCC.