Aberrantly expressed <scp>PLOD</scp>1 promotes cancer aggressiveness in bladder cancer: a potential prognostic marker and therapeutic target

Yamada, Yasutaka; Kato, Mayuko; Aoki, Takayuki; Sanada, Hiroki; Uchida, Akifumi; Misono, Shunsuke; Sakamoto, Shinichi; Komiya, Akira; Ichikawa, Tomohiko; Seki, Naohiko

doi:10.1002/1878-0261.12532

Cited by 36 publications

(38 citation statements)

References 47 publications

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“…Another study found that miR-140-5p could directly bond with the 3′-UTR of PLOD1 and decreased the expression of PLOD1 in T24 and BOY cells. Small interfering RNA-mediated PLOD1 knockdown could dramatically inhibit migration and invasion of T24 cells [ 25 ]. These results were consistent with our findings.…”

Section: Discussionmentioning

confidence: 99%

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

Jiang

Guo

Yuan

et al. 2020

BioMed Research International

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Objective. Osteosarcoma is the most common primary bone tumor and most frequently develops during adolescence. PLOD family was mainly involved in lysyl hydroxylation and rarely investigated in cancers, especially in osteosarcoma. The aim of this study was to investigate the expression pattern and oncogenic role of PLODs in osteosarcoma. Methods. GEO datasets (GSE16088, GSE33382, and GSE16091) and validation cohort were used to analyze the expression pattern of PLODs in osteosarcoma. Kaplan-Meier survival analysis was used to explore the prognostic role of PLODs in patients with osteosarcoma. RNA interference of KRT19 was performed using small interfering RNA (siRNA) in MG-63 and U-2OS cells. The proliferation was detected using CCK8, clone formation assay, and EdU staining. Migration and invasion were determined using the transwell assay. Western blots and luciferase assays for β-catenin-T-cell factor protein/β-catenin-lymphoid enhancer factor- (β-catenin-TCF/LEF-) driven transcriptional activity. Results. PLOD1 was upregulated in osteosarcoma tissues compared with control tissues both in public datasets and in in-house cohort. The expression of PLOD1 in osteosarcoma tissues was significantly associated with the status of distance metastasis and Enneking stage, while PLOD2 and PLOD3 expressed no difference between osteosarcoma and benign tissues and showed no correlation with tumor malignancy. Furthermore, Kaplan-Meier survival analysis revealed that patients with a higher level of PLOD1 had worse prognosis than those with a lower level of PLOD1. Downregulation of PLOD1 dramatically inhibited proliferation, migration, and invasion of MG-63 cells and U-2OS cells in vitro. Mechanistically, PLOD1 regulated β-catenin signaling pathway in osteosarcoma. Conclusion. Our results indicated that PLOD1 promoted proliferation, migration, and invasion of osteosarcoma cells. PLOD1 was a novel prognostic marker, as well as a therapeutic target in osteosarcoma.

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Section: Discussionmentioning

confidence: 99%

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

Jiang

Guo

Yuan

et al. 2020

BioMed Research International

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“…revealed that overexpression of PLOD1 was closely related to poor survival and downregulation of PLOD1 can decrease the progression of BC [15]. CKB was participated in metabolic processes involving glycolysis and could serve as a biomarker for predicting tumor progression [16].…”

Section: Discussionmentioning

confidence: 99%

Identification of Metabolism-associated Genes and Construction of a Prognostic Signature in Bladder Cancer

Shen

Liu

Wang

et al. 2020

Preprint

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Background Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs prognostic risk signature in BC by using The Cancer Genome Atlas (TCGA) database and proteomics data. Methods RNA-sequence data from the TCGA database and proteomics were used to identify differentially expressed MAGs and construct a prognostic MAGs signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs model in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) was further performed to investigate the expression levels of MAGs in BC cell lines and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted TGF-beta 1 in BC. Results A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that four MAGs were significantly elevated and the expression levels of three MAGs were positively correlated with M2 TAM secreted TGF-β1 in T24 cells. Conclusions Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent signature in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of three MAGs via TGF-β1 signaling pathway. Further clinical trials and experimental exploration are needed to validate our observations in BC.

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“…In addition, PLOD1 encodes lysyl hydroxylases, which are crucial for collagen biosynthesis, cross-linking, and deposition and can promote cancer progression and metastasis [39]. Yamada Y et al revealed that overexpression of PLOD1 was closely related to poor survival and downregulation of PLOD1 can decrease the progression of BC [40]. CKB was participated in metabolic processes involving glycolysis and could serve as a biomarker for predicting tumor progression [41].…”

Section: Discussionmentioning

confidence: 99%

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

Shen

Liu

Wang

et al. 2020

Preprint

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Background: Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and a high recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data. Methods: RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) were further performed to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.Results: A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features was also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAMs secreted TGF-β1 in T24 cells.Conclusions: Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental explorations are needed to validate our observations in BC.

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Aberrantly expressed PLOD1 promotes cancer aggressiveness in bladder cancer: a potential prognostic marker and therapeutic target

Cited by 36 publications

References 47 publications

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

PLOD1 Is a Prognostic Biomarker and Mediator of Proliferation and Invasion in Osteosarcoma

Identification of Metabolism-associated Genes and Construction of a Prognostic Signature in Bladder Cancer

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

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