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Cellular and Molecular Biology

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

British Journal of Cancer (2026)Cite this article

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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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Fig. 1: Mitochondrial protein SLIRP is upregulated in CRC.
The alternative text for this image may have been generated using AI.
Fig. 2: SLIRP knockdown inhibits CRC growth.
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Fig. 3: SLIRP supports CRC cell survival.
The alternative text for this image may have been generated using AI.
Fig. 4: SLIRP maintains energy metabolism homoeostasis in CRC.
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Fig. 5: SLIRP stabilises mitochondrial-encoded mRNAs (Mito-mRNAs) in CRC.
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Data availability

All data generated or analysed during this study are included in this published article and its supplementary information files.

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Acknowledgements

We thank Hao Wang (Laboratory of Dermatology, West China Hospital) for assistance with the mIHC assay; Yi Zhang and Yue Li (Core Facility, West China Hospital) for support with immunofluorescence; Selleck for providing antibodies against key energy metabolism-related proteins. Schematic diagrams were created using BioRender (https://BioRender.com).

Funding

This work was supported by the Science and Technology Foundation of Sichuan Province (2022NSFSC1296), National Natural Science Foundation of China (82102982), and the 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (ZYGD23027).

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Authors and 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

    Chenyu Yang, Yue Ming, Zixia Ye, Yingying Duan, Hulin Ma, Xiaomin Xu, Rong Wei, Xingyang Qiu, Huaping Yang, Yang Yang, Jiawei Guo & Yong Peng

  2. Colorectal Cancer Center, West China Hospital, Sichuan University, Chengdu, China

    Qingbin Wu

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Contributions

J.W.G. and Y.P. designed experiments and supervised the study. C.Y.Y., J.W.G., Y.M., Z.X.Y., Y.Y.D., H.L.M., X.M.X., R.W., X.Y.Q., H.P.Y., and Y.Y. performed experiments. Q.B.W. collected clinical samples; C.Y.Y., J.W.G., and Y.P. analysed data and prepared the manuscript. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Jiawei Guo or Yong Peng.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All animal experiments were approved by the Ethics Committee of West China Hospital, Sichuan University (Approval no. 20250408004). Human CRC and matched adjacent normal tissues were obtained from West China Hospital, Sichuan University, with ethical approval (No. 2019(540)) and informed consent from all patients. All methods were performed in accordance with the relevant guidelines and regulations.

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Yang, C., Ming, Y., Wu, Q. et al. SLIRP maintains energy metabolism homeostasis in colorectal cancer by stabilizing mitochondrial-encoded mRNAs. Br J Cancer (2026). https://doi.org/10.1038/s41416-026-03453-7

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