Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 increases cellular proliferation and colony formation capacity in lung cancer via activation of E2F transcription factor 1.

Abstract

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is an enzyme that catalyzes the hydroxylation of lysyl residues in collagen-like peptides, and is responsible for the stability of intermolecular crosslinks. High PLOD1 mRNA levels have been determined to be prognostically significant in numerous human malignancies. The objective of the present study was to elucidate the pathological mechanism of PLOD1 in lung cancer. The expression status and prognostic value of PLOD1 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSA) were investigated using Gene Expression Profiling Interactive Analysis (GEPIA). Cell Counting Kit 8 and colony formation assays were performed to assess the impact of PLOD1 depletion and overexpression on the proliferation and colony formation abilities of the A549 lung cancer cell line. Luciferase reporter assays were used to clarify whether E2F transcription factor 1 (E2F1) was a downstream target of PLOD1 in lung cancer. Finally, the correlations between PLOD1 expression and a typical central downstream effector molecule of E2F1 signaling were determined using cBioportal. The GEPIA datasets revealed that PLOD1 mRNA levels were upregulated in LUAD and LUSC samples. Furthermore, the overexpression of PLOD1 promoted cancer cell proliferation and colony formation in vitro, while PLOD1-knockout produced the opposite effect. Notably, PLOD1 markedly induced the transcriptional activity of E2F1. Additionally, the expression of PLOD1 was significantly correlated with that of H2A histone family member X. In conclusion, the findings of the present study indicate that PLOD1 promoted lung cancer through E2F1 activation, and proposed a rationale for targeting the PLOD1/E2F1 axis to treat lung cancer.