CSRNP1 Promotes Apoptosis and Mitochondrial Dysfunction via ROS-Mediated JNK/p38 MAPK Pathway Activation in...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Hepatocellular carcinoma (HCC) presents a significant global health challenge, contributing to high cancer-related mortality.
• Understanding the molecular mechanisms driving HCC development is crucial for effective treatment strategies.

Purpose of the Study:

• To identify key genes implicated in HCC pathogenesis.
• To elucidate the roles of these genes, particularly focusing on mitochondrial function and apoptosis.
• To develop a prognostic model for HCC.

Main Methods:

• Differential gene expression analysis across multiple HCC datasets (TCGA-LIHC, GSE36076, GSE95698).
• Construction of a prognostic risk model using identified differentially expressed genes (DEGs).
• Functional assays including Western blot, qRT-PCR, CCK-8, Transwell, flow cytometry, and transmission electron microscopy to assess CSRNP1 function and related pathways.

Main Results:

• A six-gene prognostic model was developed, including downregulated genes (NR4A1, CSRNP1) and upregulated genes (CENPQ, YAE1, FANCF, POC5).
• CSRNP1 knockdown enhanced HCC cell proliferation and inhibited apoptosis.
• CSRNP1 overexpression impaired mitochondrial integrity, increased reactive oxygen species (ROS) levels, and activated the JNK/p38 MAPK pathway.

Conclusions:

• CSRNP1 functions as a novel tumor suppressor in HCC.
• CSRNP1 exerts anti-tumor effects via induction of oxidative stress and activation of the ROS-dependent JNK/p38 MAPK pathway.
• CSRNP1 represents a potential therapeutic target for managing HCC.