2021.11.30 Peng Liyuan's research results were published in the authoritative academic journal Cell Reports

On November 30, 2021, our student Peng Liyuan published a research paper entitled "Redox-sensitive cyclophilin A elicits chemoresistance through realigning cellular oxidative status in colorectal cancer" in the international authoritative academic journal Cell Reports (impact factor 9.7). Peng Liyuan is the first author of the paper, and the joint first author is Dr. Jiang Jingwen, and our supervisor Professor Huang Canhua is the corresponding author of the article. In addition, the work was also supported by Academician Wei Yuquan, Director of the State Key Laboratory of Biotherapeutics of Sichuan University, Professor Liu Yicheng (Yih-Cherng Liou) and Professor Deng Liwen (Lih-Wen Deng) of the National University of Singapore, and Edouard C. Professor Nice and Associate Professor Chen Haining of the Department of Gastrointestinal Surgery of West China Hospital of Sichuan University.

Oxidative stress and antioxidant response participate in the whole process of tumorigenesis and development, and play an important regulatory role in the process of tumor drug resistance and dry character maintenance. Classical antioxidant systems in cells include antioxidant transcription factors (Nrf2, FOXOs, etc.), non-catalytic reducing power (GSH, NADPH, etc.), catalytic antioxidants (PRDXs, TRXs, etc.), etc. In addition, some high-abundance redox proteins (Albumin, Mucin, etc.) can buffer oxidative stress through the non-classical antioxidant pathway mediated by autoredox modification. However, how the non-classical antioxidant pathway mediated by redox proteins regulates tumor resistance remains unclear.

Using the redox proteomics database, drug target database and tumor-related database, combined with bioinformatics analysis, we found that cyclophilin A (CypA) is a potential redox protein associated with drug resistance in colorectal cancer. Further studies have shown that the redox protein CypA can mediate a non-classical antioxidant pathway through redox modification involving PRDX2, thereby remodeling the oxidative state of colorectal cancer cells, leading to their chemotherapy resistance. CypA and PRDX2 are highly expressed in the tissues of drug-resistant patients and are significantly associated with poor prognosis. Inhibition of CypA by CsA can break the redox homeostasis of colorectal cancer, thereby increasing the sensitivity of colorectal cancer to chemotherapy drugs, suggesting that redox protein CypA is expected to become a drug target for reversing chemotherapy resistance in colorectal cancer in clinic. These findings shed light on the molecular mechanism of CypA-PRDX2 nonclassical antioxidant pathway mediating chemotherapy resistance in colorectal cancer, providing a potential combination regimen for clinical reversal of chemotherapy resistance in colorectal cancer.

Article link: https://doi.org/10.1016/j.celrep.2021.110069

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