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

Abstract

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.

A Human Pan-Cancer System Analysis of Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase 3 (PLOD3)

“…Considering the essential role of PLOD3, and the encoded enzyme, in the formation of the extracellular matrix derived from fibroblasts, chondroblasts and osteoblasts, we were not surprised that it could also be overexpressed in connective tissue malignancies (SARC), compared to corresponding normal tissue, according to the immunohistochemical analyses. Considering the findings of Jiang et al, that PLOD1 is a prognostic marker in osteosarcomas [ 68 ]. Further studies, especially of soft tissue sarcomas, are pending.…”

Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase Family: Novel Prognostic Biomarkers and Tumor Microenvironment Regulators for Lower-Grade Glioma

“…Deposition and cross-linking of collagen within the ECM offer a chemical and physical support for tumor formation and proliferation (Qi and Xu, 2018). Three members of the PLOD family (i.e., PLOD1, PLOD2, and PLOD3) leading to cancer progression and metastasis when dysregulated have already been identified (Jiang et al, 2020;Li S. S. et al, 2020). It has recently been recognized that PLOD1 is overexpressed in glioma (Tian et al, 2021).…”

PLOD1 promotes cell growth and aerobic glycolysis by regulating the SOX9/PI3K/Akt/mTOR signaling pathway in gastric cancer

“…The expression of both PLOD1 mRNA and protein in clear cell renal cell carcinoma (ccRCC) tissues was significantly higher than that in normal kidney tissues; further studies showed that the increased PLOD1 mRNA level was relate to high pathological grade, advanced tumor stage, shorter progression-free and overall survival rate [31]. PLOD1 expression was increased in osteosarcoma tissues, which was closely linked to distance metastasis and Enneking stage, and worse prog-nosis; silencing of PLOD1 resulted in obvious inhibitions on cell growth, movement, and invasiveness of MG-63 cells and U-2OS cells [20,32]. In the current study, we used plasmids and shRNAs to upregulate and downregulate PLOD1 expression in GC cells AGS and HGC-27 with medium It has been well documented that tumor cells can obtain adequate energy through metabolic stress to meet the rapid growth of tumor cells, including GC [33,34].…”