Regulatory Role of the RUNX2 Transcription Factor in Lung Cancer Apoptosis

Camila Bernal, Andrea Otalora, Alejandra Cañas, Alfonso Barreto, Karol Prieto, Martin Montecino, Adriana Rojas

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Lung cancer is the leading cause of cancer death globally. Numerous factors intervene in the onset and progression of lung tumors, among which the participation of lineage-specific transcription factors stands out. Several transcription factors important in embryonic development are abnormally expressed in adult tissues and thus participate in the activation of signaling pathways related to the acquisition of the tumor phenotype. RUNX2 is the transcription factor responsible for osteogenic differentiation in mammals. Current studies have confirmed that RUNX2 is closely related to the proliferation, invasion, and bone metastasis of multiple cancer types, such as osteosarcoma, breast cancer (BC), prostate cancer, gastric cancer, colorectal cancer, and lung cancer. Thus, the present study is aimed at evaluating the role of the RUNX2 transcription factor in inhibiting the apoptosis process. Loss-of-function assays using sh-RNA from lentiviral particles and coupled with Annexin/propidium iodide (PI) assays (flow cytometry), immunofluorescence, and quantitative PCR analysis of genes related to cell apoptosis (BAD, BAX, BCL2, BCL-XL, and MCL1) were performed. Silencing assays and Annexin/PI assays demonstrated that when RUNX2 was absent, the percentage of dead cells increased, and the expression levels of the BCL2, BCL-XL, and MCL1 genes were downregulated. Furthermore, to confirm whether the regulatory role of RUNX2 in the expression of these genes is related to its binding to the promoter region, we performed chromatin immunoprecipitation (ChIP) assays. Here, we report that overexpression of the RUNX2 gene in lung cancer may be related to the inhibition of the intrinsic apoptosis pathway, specifically, through direct transcriptional regulation of the antiapoptotic gene BCL2 and indirect regulation of BCL-XL and MCL1.

Original languageEnglish
Article number5198203
JournalInternational Journal of Cell Biology
Volume2022
DOIs
Publication statusPublished - 2022

ASJC Scopus subject areas

  • Cell Biology

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