SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs
Menée à l'aide de lignées cellulaires, de xénogreffes sur des modèles murins ainsi que d'échantillons tumoraux et d'échantillon de tissus adjacents normaux prélevés sur des patients atteints d'un cancer colorectal, cette étude met en évidence un mécanisme par lequel la protéine SLIRP maintient la phosphorylation oxydative de la tumeur en stabilisant les ARN messagers issus de l'ADN mitochondrial
Background : Colorectal cancer (CRC) is a highly vascularised tumour often characterised by elevated oxidative phosphorylation (OXPHOS) activity, positioning OXPHOS as a potential metabolic vulnerability for targeted therapy. SLIRP is an RNA-binding protein involved in the post-transcriptional regulation of mitochondrial gene expression. However, its specific function and underlying mechanism in CRC remain poorly understood.
Methods : Clinical specimens and public databases were utilised to analyse both the subcellular localisation and expression of SLIRP in CRC. The functional role of SLIRP in CRC progression was assessed through cell growth, apoptosis, and metabolic analyses. Post-transcriptional regulation of mitochondrial-encoded mRNAs by SLIRP was investigated using RNA immunoprecipitation and mRNA stability assays.
Results : SLIRP expression was significantly elevated in CRC tissues compared to adjacent normal tissues, and high SLIRP expression correlated with poor patient survival. SLIRP knockdown induced an ATP crisis, leading to suppressed tumour growth and increased apoptosis in CRC cells. Mechanistically, SLIRP globally binds to mitochondrial-encoded mRNAs and maintains their stability, functioning as a key post-transcriptional regulator of mitochondrial gene expression.
Conclusions : These findings uncover a critical role for SLIRP in maintaining OXPHOS activity in CRC and highlight its potential as both a prognostic biomarker and a therapeutic metabolic target.
British Journal of Cancer , article en libre accès, 2026