4.7 Article

Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells

Journal

BIOMEDICINES
Volume 10, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10123122

Keywords

lung cancer (LC); differentially expressed genes (DEGs); transcription factors (TFs); coexpression networks; gene regulatory network (GRN); diagnostic and prognostic biomarkers

Funding

  1. National University of Colombia [41492]
  2. Pontificia Universidad Javeriana [PUJ ID7687]

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The use of a new bioinformatics pipeline identified deregulated transcription factors in lung cancer, with RUNX2 potentially playing a key role in the gene regulatory network. Experimental validation of RUNX2's regulatory function could lead to its use as a biomarker for diagnostic tools and specific treatments against lung tumoral diseases.
The use of a new bioinformatics pipeline allowed the identification of deregulated transcription factors (TFs) coexpressed in lung cancer that could become biomarkers of tumor establishment and progression. A gene regulatory network (GRN) of lung cancer was created with the normalized gene expression levels of differentially expressed genes (DEGs) from the microarray dataset GSE19804. Moreover, coregulatory and transcriptional regulatory network (TRN) analyses were performed for the main regulators identified in the GRN analysis. The gene targets and binding motifs of all potentially implicated regulators were identified in the TRN and with multiple alignments of the TFs' target gene sequences. Six transcription factors (E2F3, FHL2, ETS1, KAT6B, TWIST1, and RUNX2) were identified in the GRN as essential regulators of gene expression in non-small-cell lung cancer (NSCLC) and related to the lung tumoral process. Our findings indicate that RUNX2 could be an important regulator of the lung cancer GRN through the formation of coregulatory complexes with other TFs related to the establishment and progression of lung cancer. Therefore, RUNX2 could become an essential biomarker for developing diagnostic tools and specific treatments against tumoral diseases in the lung after the experimental validation of its regulatory function.

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