High Expression of<i>PLOD1</i>Drives Tumorigenesis and Affects Clinical Outcome in Gastrointestinal Carcinoma

Wang, Dazhi; Zhang, Shuyu; Fufeng, Chen

doi:10.1089/gtmb.2018.0009

Cited by 31 publications

(33 citation statements)

References 22 publications

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“…The procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 1 gene (PLOD1) is about 41 kb in size and located on chromosome 1p36.2‐36.3.The 19 exons encode 727 amino acid residue containing enzyme lysyl hydroxylase (LH1, procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 1; EC 1.14.11.4), which is a membrane‐bound homodimeric protein localized to the cisternae of endoplasmic reticulum . The enzyme (cofactors iron and ascorbate) promotes the hydroxylation of lysine in collagens and obtains hydroxyl groups, the binding sites of carbohydrates in collagen; thus, it is critical for intermolecular crosslinks and morphogenesis of organs and tissues .…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have proved that the deficiency of lysyl hydroxylase activity plays an important role in Ehlers‐Danlos syndrome type VI . Moreover, high expression of PLOD1 has been found to closely related with tumorigenesis and development of tumors, while negatively correlated with clinical outcome in gastrointestinal carcinoma such as esophageal squamous cell carcinoma, gastric cancers, and colon cancer . Besides, the expression of PLOD1 was also associated with drug resistance and metastasis of breast cancer .…”

Section: Discussionmentioning

confidence: 99%

“…14.11.4), which is a membrane-bound homodimeric protein localized to the cisternae of endoplasmic reticulum. 31,32 The enzyme (cofactors iron and ascorbate) promotes the hydroxylation of lysine in collagens and obtains hydroxyl groups, the binding sites of carbohydrates in collagen; thus, it is critical for intermolecular crosslinks and morphogenesis of organs and tissues. 31,33 Several studies have proved that the deficiency of lysyl hydroxylase activity plays an important role in Ehlers-Danlos syndrome type VI.…”

Section: Discussionmentioning

confidence: 99%

“…34,35 Moreover, high expression of PLOD1 has been found to closely related with tumorigenesis and development of tumors, while negatively correlated with clinical outcome in gastrointestinal carcinoma such as esophageal squamous cell carcinoma, gastric cancers, and colon cancer. 32,36 Besides, the expression of PLOD1 was also associated with drug resistance and metastasis of breast cancer. 33 In the TSCC samples obtained from GSE31056, we found that PLOD1 was a candidate hub gene associated with tumor occurrence, recurrence, and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Transcripto‐based network analysis reveals a model of gene activation in tongue squamous cell carcinomas

Zeng

Zhao

et al. 2019

Head & Neck

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Background Tongue squamous cell carcinoma (TSCC) is the most common malignant tumor derived from the oral cavity, yet its specific molecular mechanisms have not been fully clarified. The aim of this study was to evaluate the association between potential genes and clinical features through constructing gene co‐expression networks. Methods The weighted gene co‐expression network analysis was used to construct gene co‐expression networks and to identify candidate key modules and hub genes. The gene expression profiles of GSE31056 obtained from the Gene Expression Omnibus (GEO) database was used to construct co‐expression networks. Results Five hub genes (FAP, AGTRAP, PLOD1, POSTN, and TSHZ3) were identified and validated at transcriptional levels. Moreover, the protein levels of these five hub genes were also found significantly higher in tumor tissues. Among them, FAP was most associated with immune infiltration. Conclusions These five candidate biomarkers and therapeutic targets are worthy of further investigation and discussion.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Transcripto‐based network analysis reveals a model of gene activation in tongue squamous cell carcinomas

Zeng

Zhao

et al. 2019

Head & Neck

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“…Here, high-level PLOD1/2/3 expression was strongly linked to advanced pathological tumor stage and overall survival. Moreover, PLOD1/2/3 were also reported to be associated with several other solid tumors, such as gastrointestinal carcinoma and glioma [ 15 , 16 ], while the expression and prognostic role of PLODs in osteosarcoma remain to be further illustrated.…”

Section: Introductionmentioning

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

et al. 2019

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Bladder cancer ( BC ) is the ninth most malignant tumor worldwide. Some BC patients will develop muscle‐invasive BC ( MIBC ), which has a 5‐year survival rate of approximately 60% due to metastasis. As such, there is an urgent need for novel therapeutic and diagnostic targets for MIBC . Analysis of novel antitumor micro RNA (mi RNA )‐mediated cancer networks is an effective strategy for exploring therapeutic targets and prognostic markers in cancers. Our previous mi RNA analysis revealed that miR‐140‐5p acts as an antitumor mi RNA in BC cells. Here, we investigated miR‐140‐5p regulation of BC molecular pathogenesis. Procollagen‐lysine, 2‐oxoglutarate 5‐dioxygenase 1 ( PLOD 1 ) was found to be directly regulated by miR‐140‐5p , and aberrant expression of PLOD 1 was observed in BC clinical specimens. High PLOD 1 expression was significantly associated with a poor prognosis (disease‐free survival: P = 0.0204; overall survival: P = 0.000174). Multivariate analysis showed PLOD 1 expression to be an independent prognostic factor in BC patients (hazard ratio = 1.51, P = 0.0099). Furthermore, downregulation of PLOD 1 by si RNA s and a specific inhibitor significantly decreased BC cell aggressiveness. Aberrant expression of PLOD 1 was closely associated with BC pathogenesis. In summary, the present study showed that PLOD 1 may be a potential prognostic marker and therapeutic target for BC .

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High Expression ofPLOD1Drives Tumorigenesis and Affects Clinical Outcome in Gastrointestinal Carcinoma

Abstract: These results indicated that PLOD1 is highly expressed in gastrointestinal carcinoma and is a potential prognostic marker and therapeutic target. The data also indicate that hypomethylation contributes to PLOD1 upregulation in gastric and colon cancers.

Cited by 31 publications

References 22 publications

Transcripto‐based network analysis reveals a model of gene activation in tongue squamous cell carcinomas

Transcripto‐based network analysis reveals a model of gene activation in tongue squamous cell carcinomas

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

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

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