Cyclophilin A is a factor of antitumor defense in the early stages of tumor development

Kalinina, Anastasiia; Голубева, И. С.; Kudryavtsev, I. V.; Khromova, N.; Antoshina, Elena; Trukhanova, Lubov; Gorkova, Tatyana; Kazansky, Dmitry; Хромых, Л. М.

doi:10.1016/j.intimp.2021.107470

Cited by 12 publications

(8 citation statements)

References 49 publications

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“…In our analysis, intense PPIA expression was observed in most of the LUAD tissues, while limited expression was shown in the peritumoral tissues.The high expression of PPIA was related to the poor survival of LUAD patients,which was consistent with the correlation between the overexpression of PPIA and the overall survival of liver hepatocellular carcinoma and colorectal cancer [21,22].ROC curve analysis indicated that PPIA could be a promising diagnostic biomarker to differentiate LUAD from normal tissues.In addition,the progression of LUAD may be associated with the upregulation of PPIA.Notably,the expression of PPIA was positively correlated with high N stage,high pathological stage.Patients with LUAD with higher expression levels of PPIA exhibited signi cantly shorter overall survival times.The increased expression of PPIA in LUAD with pathological stage of III/IV and lymph node metastasis further indicates that PPIA may be involved in the progression and malignant transformation of LUAD. In subgroup analyses, patients of LUAD with high PPIA expression had shorter OS than patients with low PPIA levels and were characterized by TNM stage,pathological stage,male and female,whole age,anatomic neoplasm subdivision of left and peripheral,smoke and non-smoke,smoked for less than 40 years.In M0 stage,the OS was shorter in patients with high expression of PPIA, while in the M1 phase, the epitopes of PPIA were not correlated with OS,which may be related to the aforementioned viewpoint that the anti-tumor properties of CypA may be more effective in the initial stages of cancer development [27].The current results indicated that PPIA may serve as a biomarker for the progress of LUAD.Therefore, in clinical work, LUAD patients with high expression of PPIA have a higher risk of recurrence, and follow-up examinations should be performed more frequently.…”

Section: Discussionmentioning

confidence: 91%

“…The cytoprotective effect of PPIA seems to depend on its PPIase activity [26]. Other study indicated that PPIA as one of the factors of antitumor host defense that can effectively control the initial stages of tumor and metastases formation by regulating the action of MMPs(matrix metalloproteinases) and changing the tumor microenvironment [27]. therefore the question remains unanswered as to whether PPIA could serve as a prognostic factor and potential target for therapy in the future.…”

Section: Introductionmentioning

confidence: 99%

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Identification Of PPIA As A Prognostic Biomarker Of Lung Adenocarcinoma From Bioinformatics Analysis

Chen

et al. 2022

Preprint

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Background: We aim to investigate the expression of the peptidylprolyl isomerase A (PPIA) gene in lung adenocarcinoma(LUAD),and to investigate the diagnostic, prognostic value and correlation with immune infiltrates of PPIA in LUAD.Methods: Transcriptional expression profiles of PPIA between LUAD tissues and normal tissues were downloaded from the Cancer Genome Atlas (TCGA).The PPIA protein expression was assessed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC) .Receiver operating characteristic(ROC) curve was used to differentiate LUAD from adjacent normal tissues.Kaplan-Meier method was conducted to assess the effect of PPIA on survival.Protein-protein interaction (PPI) networks were constructed by the STRING.Functional enrichment analyses were performed using the“ClusterProfiler”package.The relationship between PPIA mRNA expression and immune infiltrates was determined by tumor immune estimation resource (TIMER) and tumor-immune system interaction database (TISIDB).Results: The expression of PPIA in LUAD tissues was significantly upregulated than those in adjacent normal tissues. High PPIA mRNA expression was associated with lymph node metastases and high TNM stage. The ROC curve analysis showed that PPIA had an AUC value of 0.804(95% CI: 0.764-0.843).Kaplan-Meier survival analysis showed LUAD patients with high-PPIA had a worse prognosis than those with low-PPIA(mOS: 42.2months VS 87.2months,P＜0.001). Correlation analysis indicated PPIA mRNA expression was correlated with immune infiltrates.PPIA expression had correlations with CD4+ T cell (r = -0.29, P = 5.51e-11),macrophage M1 (r = 0.106, P = 1.84e-02), and B cell (r = -0.181, P =5.40e-5).Conclusion: Our research showed that PPIA could be used as a prognostic biomarker.Up-regulation of PPIA expression is significantly related to poor prognosis and immune infiltration of LUAD and may be a potential therapeutic molecular target for LUAD patients.

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Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Identification Of PPIA As A Prognostic Biomarker Of Lung Adenocarcinoma From Bioinformatics Analysis

Chen

et al. 2022

Preprint

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“…Mice were administered the calculated amount of inhibitor by subcutaneous injection into the cervical fold once every 7 days, on days 7 and 14 following melanoma cell transplantation. On day 15, which corresponds to the end of the pre-metastatic period and the beginning of the metastatic period of transplanted melanoma [ 20 ], the animals were sacrificed.…”

Section: Methodsmentioning

confidence: 99%

miR-204-5p in vivo inhibition cause diminished CD45RO cells rate in lungs of melanoma B16-bearing mice

Palkina

Aksenenko

Zemtsov

et al. 2022

Non-coding RNA Research

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“…CypA is involved in oxidative stress-mediated neurodegenerative diseases, rheumatoid arthritis, sepsis, and aging [ 29 , 30 , 31 , 32 ]. CypA alters the tumor microenvironment by promoting the development of Th1 immune responses through modulation of matrix metalloproteinase (MMP) and induction of proinflammatory cytokines such as tumor necrosis factor alpha (TNFα) and interferon gamma (IFNγ) and thus may control the early stages of tumor and metastasis formation [ 33 ]. CypA is overexpressed in many cancers and promotes cancer cell proliferation, anti-apoptosis, and metastasis/infiltration [ 34 , 35 , 36 ].…”

Section: Biological Functions Of Cypa and Cd147mentioning

confidence: 99%

“…The roles of CypA and CD147 in cancer development were studied ( Figure 4 and Table 1 ). They are upregulated in various types of cancers and have been identified as crucial mediators of tumorigenesis and cancer cell proliferation [ 33 , 54 , 55 , 56 , 57 , 58 ]. Hypoxia-inducible factor (HIF)-1α, activated by hypoxia, can promote the expression and autocrine secretion of CypA, leading to cancer growth [ 36 , 56 ].…”

Section: Roles Of Cypa/cd147 Interaction In Cancermentioning

confidence: 99%

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

Han

Jung

2022

IJMS

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Cyclophilin A (CypA), which has peptidyl–prolyl cis-trans isomerase (PPIase) activity, regulates multiple functions of cells by binding to its extracellular receptor CD147. The CypA/CD147 interaction plays a crucial role in the progression of several diseases, including inflammatory diseases, coronavirus infection, and cancer, by activating CD147-mediated intracellular downstream signaling pathways. Many studies have identified CypA and CD147 as potential therapeutic targets for cancer. Their overexpression promotes growth, metastasis, therapeutic resistance, and the stem-like properties of cancer cells and is related to the poor prognosis of patients with cancer. This review aims to understand the biology and interaction of CypA and CD147 and to review the roles of the CypA/CD147 interaction in cancer pathology and the therapeutic potential of targeting the CypA/CD147 axis. To validate the clinical significance of the CypA/CD147 interaction, we analyzed the expression levels of PPIA and BSG genes encoding CypA and CD147, respectively, in a wide range of tumor types using The Cancer Genome Atlas (TCGA) database. We observed a significant association between PPIA/BSG overexpression and poor prognosis, such as a low survival rate and high cancer stage, in several tumor types. Furthermore, the expression of PPIA and BSG was positively correlated in many cancers. Therefore, this review supports the hypothesis that targeting the CypA/CD147 interaction may improve treatment outcomes for patients with cancer.

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Cyclophilin A is a factor of antitumor defense in the early stages of tumor development

Cited by 12 publications

References 49 publications

Identification Of PPIA As A Prognostic Biomarker Of Lung Adenocarcinoma From Bioinformatics Analysis

Identification Of PPIA As A Prognostic Biomarker Of Lung Adenocarcinoma From Bioinformatics Analysis

miR-204-5p in vivo inhibition cause diminished CD45RO cells rate in lungs of melanoma B16-bearing mice

Cyclophilin A/CD147 Interaction: A Promising Target for Anticancer Therapy

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