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The role of PYCR1 in inhibiting 5-fluorouracil-induced ferroptosis and apoptosis through SLC25A10 in colorectal cancer

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Abstract

Although PYCR1 is a well-recognized oncogenic gene for malignant tumors, the causal relationship of its expression with malignant growth and cytotoxic chemotherapeutics remains unclear. Therefore, this study aimed to clarify the role of PYCR1 and its interaction with SLC25A10 in a chemotherapeutic agent 5-fluorouracil (5-FU)’s toxicity to colorectal cancer cells. PYCR1 and SLC25A10 expressions were detected in The Cancer Genome Atlas database and colon adenocarcinoma (COAD) clinical samples. PYCR1 upregulation was associated with SLC25A10 expression and poor prognosis, and its high expression indicated decreased survival rates in patients with COAD. PYCR1 overexpression inhibited lipid reactive oxygen species production and promoted SLC25A10 expression in colorectal cancer cells. PYCR1 silencing enhanced the antitumor effects of 5-FU. Ferroptosis inhibitor deferoxamine suppressed the antitumor effects of PYCR1 silencing, whereas ferroptosis inducer erastin inhibited the protumor effects of PYCR1 overexpression. SLC25A10 overexpression reversed the antitumor effects of PYCR1 silencing in vitro and inhibited the antitumor effects of erastin in vivo. Therefore, PYCR1 is an oncogenic gene that promotes colorectal tumor growth and desensitizes colorectal cancer cells to 5-FU cytotoxicity by preventing apoptosis and ferroptosis.

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Funding

This study was supported by Science and Technology Development Fund Of Shanghai Pudong New Area (PKJ2020-Y15), The leading talent Training Program of Pudong Health Bureau of Shanghai (PWRl2019-03), Excellent subject leader training project of the three-year action plan of Shanghai public health system (GWV-10.2-XD15) and Key discipline construction project of the three-year action plan of Shanghai public health system (GWV-10.1-XK9).

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Author notes

  1. Borong Zhou and Zhongchao Mai contributed equally.

Authors and Affiliations

  1. Department of Nuclear Medicine, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, No. 358 Datong Road, Pudong New District, Shanghai, 200137, China

    Borong Zhou, Zhongchao Mai, Xinlin Yang & Wei Xia

  2. Central Laboratory, The Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Ying Ye, Yanan Song & Miao Zhang

  3. Department of Gastrointestinal Surgery, The Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

    Xiaofeng Qiu

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  1. Borong Zhou
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  2. Zhongchao Mai
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  3. Ying Ye
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  4. Yanan Song
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  5. Miao Zhang
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  6. Xinlin Yang
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  7. Wei Xia
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Contributions

Conceptualization: WX, XQ; methodology: BZ, ZM, XY; formal analysis and investigation: BZ, ZM, YY, YS, MZ; writing—original draft preparation: BZ, ZM; writing—review and editing: WX, XQ, YY; supervision: WX, XQ.

Corresponding authors

Correspondence to Wei Xia or Xiaofeng Qiu.

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Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional Ethical Review Committee of The Seventh People’s Hospital (Shanghai, China; approval number: 2022-7th-HIRB-025 for human subjects and 2022-011 for animal experiments).

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Zhou, B., Mai, Z., Ye, Y. et al. The role of PYCR1 in inhibiting 5-fluorouracil-induced ferroptosis and apoptosis through SLC25A10 in colorectal cancer. Human Cell 35, 1900–1911 (2022). https://doi.org/10.1007/s13577-022-00775-5

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  • DOI: https://doi.org/10.1007/s13577-022-00775-5

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