SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs

  • Br J Cancer. 2026 Aug;135(3):349-360. doi: 10.1038/s41416-026-03453-7.
Chenyu Yang  1 ,  Yue Ming  1 ,  Qingbin Wu  2 ,  Zixia Ye  1 ,  Yingying Duan  1 ,  Hulin Ma  1 ,  Xiaomin Xu  1 ,  Rong Wei  1 ,  Xingyang Qiu  1 ,  Huaping Yang  1 ,  Yang Yang  1 ,  Jiawei Guo  3 ,  Yong Peng  4
Affiliations
  • 1. Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 2. Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  • 3. Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [email protected].
  • 4. Center for Molecular Oncology, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [email protected].
PMID: 42049860 DOI: 10.1038/s41416-026-03453-7
Abstract

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.

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