ArticleScientific reports2025
Cyclophilin D suppresses colorectal cancer progression through the activation of an autophagy-mediated apoptotic pathway.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Abstract
Colorectal cancer (CRC) remains a leading gastrointestinal malignancy and lacks effective adjuvant therapies. Cyclophilin D (CypD), a mitochondrial matrix protein, has a controversial role in tumorigenesis. While prior studies suggest a CypD-CRC link, its precise function and mechanisms remain undefined. Here we clarify whether CypD acts as a driver or suppressor of CRC and explore its therapeutic implications. Using RT-qPCR, Western blotting, and immunofluorescence, we confirmed significant CypD downregulation in CRC tissues/cells versus non-malignant controls. Through in vitro (CCK-8, colony formation, transwell migration, spheroid formation, apoptosis, and autophagy assays) and in vivo tumor xenograft experiments with CypD-knockdown/overexpressing CRC cells (DLD1 and RKO), knocking down CypD promoted, whereas its overexpression inhibited, malignant phenotypes (proliferation, migration, self-renewal, tumorigenicity). Mechanistically, CypD activated protective autophagy and cell apoptosis, with autophagy inhibitor chloroquine reversing this effect. Critically, knocking down CypD attenuated the anti-CRC efficacy of 5-fluorouracil/epigallocatechin-3-gallate combination therapy, whereas its overexpression enhanced therapeutic response. This study provides the first definitive evidence that CypD functions as a tumour suppressor via autophagy-apoptosis crosstalk. Low CypD expression may serve as a biomarker for poor treatment response. Enhancing CypD activity represents a promising strategy to augment existing CRC treatments.
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