# MRPL17 is a critical regulator of mitochondrial function and a novel therapeutic target in non-small cell lung cancer

## TL;DR

MRPL17 promotes non-small cell lung cancer by enhancing mitochondrial function and is a potential new treatment target.

## Contribution

MRPL17 is identified as a novel therapeutic target in NSCLC through its regulation of mitochondrial function and COX8A.

## Key findings

- MRPL17 is significantly upregulated in LUAD and LUSC tumor tissues and correlates with poor prognosis.
- MRPL17 silencing reduces NSCLC cell viability and proliferation while impairing mitochondrial function.
- COX8A is confirmed as a direct downstream target of MRPL17, mediating its pro-cancerous effects.

## Abstract

This study investigated the role of the mitochondrial protein MRPL17 (mitochondrial ribosomal protein L17) in non-small cell lung cancer (NSCLC), exploring its expression profile, clinical significance, and therapeutic potential. Transcriptomic analyses of TCGA and single-cell RNA sequencing data revealed significant upregulation of MRPL17 in LUAD (lung adenocarcinoma) and LUSC (lung squamous cell carcinoma) tumor tissues, particularly within malignant epithelial and proliferating cancer cells. Elevated MRPL17 expression correlated with advanced stages, positive lymph node metastasis, and poorer overall survival. In vitro investigations demonstrated that silencing or knockout of MRPL17 attenuated cell viability, proliferation, migration, and invasion in NSCLC cells, while promoting apoptosis. Mechanistically, MRPL17 silencing impaired mitochondrial respiratory function, causing reduced oxygen consumption, diminished Complex I activity, and decreased ATP. These impairments were partially reversible by antioxidant treatment or glucose supplementation. Conversely, MRPL17 overexpression enhanced aggressive cellular phenotypes and mitochondrial energetic output. Bioinformatic analysis and subsequent experiments confirmed COX8A as a direct downstream target of MRPL17, mediating its pro-cancerous effects. In vivo, MRPL17 silencing suppressed NSCLC xenograft growth in nude mice, a phenomenon associated with reduced COX8A levels, mitochondrial dysfunction, heightened oxidative stress, and increased apoptosis. Thus, MRPL17 is an important pro-cancerous target in NSCLC, driving malignant progression through the regulation of mitochondrial function and cellular redox balance, with COX8A identified as a key mediator.