Evidence map›Paper›PMID 41454054›Full record

ArticleScientific reports2025

Cyclophilin D suppresses colorectal cancer progression through the activation of an autophagy-mediated apoptotic pathway.

Ling Zhang, Yi Liu, Ruiqi Liu, Wenjun Wang, Ruiji Li

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Ling ZhangSchool of Nursing, Jining Medical University, Jining, 272067, Shandong, China.
Yi LiuSchool of Public Health, North China University of Science and Technology, Tangshan, 063210, Hebei, China.
Ruiqi LiuBiobank, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, 710004, Shaanxi, China.
Wenjun WangWeifang Nursing Vocational College, Qingzhou, 262500, Shandong, China. wwjun1973@163.com.
Ruiji LiSchool of Pharmacy, Jining Medical University, Rizhao, 276826, Shandong, China. li-ruiji@mail.jnmc.edu.cn.

Funding

Natural Science Foundation of Shandong Province ZR2021QB124Natural Science Foundation of Shandong Province ZR2021QH294Outstanding Youth Foundation (Overseas) Project of Rizhao City Natural Science Foundation RZ2021ZR1Research Fund for Academician Lin He New Medicine JYHL2022MS02
6 · The paper itself

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.

Indexed as

ApoptosisAutophagyColorectal NeoplasmsCyclophilinsPeptidyl-Prolyl Isomerase FAnimalsCell Line, TumorCell MovementCell ProliferationDisease ProgressionGene Expression Regulation, NeoplasticHumansMiceMice, NudeSignal TransductionXenograft Model Antitumor AssaysCyclophilinsPeptidyl-Prolyl Isomerase FApoptosisAutophagyColorectal cancerCyclophilin DMalignant phenotype

Identifiers

PMID41454054
PMCPMC12852878

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.