MRPL47 deficiency drives mitochondrial dysfunction via ROS-p38-p21 signaling in non-small cell lung cancer

Area of Science:

• Mitochondrial Biology
• Cancer Genomics
• Molecular Oncology

Background:

• Mitoribosomes synthesize proteins crucial for cellular energy via oxidative phosphorylation.
• Mitoribosomal dysregulation is linked to cancer, but the genomic status of mitoribosomal proteins (MRPs) in nonsmall cell lung cancer (NSCLC) is unclear.

Purpose of the Study:

• To investigate the genomic landscape and functional role of MRPs in NSCLC.
• To identify potential prognostic markers and therapeutic targets in NSCLC.

Main Methods:

• Comprehensive analysis of MRP expression, copy number variations, and mutations in TCGA-NSCLC patient data.
• Functional assays including gene inhibition, cell proliferation, migration, and mitochondrial function assessments.
• Transcriptomic analysis and signaling pathway investigation (ROS-p38-p21-Rb-E2F axis).

Main Results:

• MRPL47 was identified as significantly amplified and overexpressed in NSCLC.
• MRPL47 overexpression correlated with poor patient survival across independent datasets.
• MRPL47 inhibition reduced NSCLC cell proliferation and migration, impaired oxidative phosphorylation, and induced cell cycle arrest via the ROS-p38-p21-Rb-E2F pathway.

Conclusions:

• MRPL47 is a key driver in NSCLC, acting as a prognostic marker.
• MRPL47 promotes tumor progression by disrupting mitochondrial function and altering cell cycle regulation.
• Targeting MRPL47 may offer a novel therapeutic strategy for NSCLC.