TY - JOUR
T1 - Identification of the Transcriptional Regulatory Role of RUNX2 by Network Analysis in Lung Cancer Cells
AU - Otálora-Otálora, Beatriz Andrea
AU - González Prieto, Cristian
AU - Guerrero, Lucia
AU - Bernal-Forigua, Camila
AU - Montecino, Martin
AU - Cañas, Alejandra
AU - López-Kleine, Liliana
AU - Rojas, Adriana
N1 - Publisher Copyright:
© 2022 by the authors.
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
KW - coexpression networks
KW - diagnostic and prognostic biomarkers
KW - differentially expressed genes (DEGs)
KW - gene regulatory network (GRN)
KW - lung cancer (LC)
KW - transcription factors (TFs)
UR - http://www.scopus.com/inward/record.url?scp=85144740609&partnerID=8YFLogxK
U2 - 10.3390/biomedicines10123122
DO - 10.3390/biomedicines10123122
M3 - Article
AN - SCOPUS:85144740609
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 12
M1 - 3122
ER -