The FoxP1 gene regulates lung function, production of matrix metalloproteinases and inflammatory mediators, and viability of lung epithelia

Abstract

Background Genes involved in lung development may become dysregulated in adult life and contribute to the pathogenesis of lung diseases. Multiple genes regulate lung development, including Forkhead box protein P1-4 (FoxP1-4). Methods We examined the association between variants in the FoxP1-4 genes and lung function using data from a GWAS that included close to 400,000 individuals and 20 million SNPs. Results More than 100 variants in the FoxP1 gene, but none in the FoxP2-4 genes, are associated with lung function. The sentinel variant in the FoxP1 gene associated with FEV1 was rs1499894 (C > T), while the sentinel variant in the FoxP1 gene associated with FVC was rs35480566 (A > G). Those with the T allele instead of the C allele for rs1499894, or the G allele instead of the A allele for rs35480566 had increased FoxP1 mRNA levels in transcriptomic data, higher FEV1 and FVC, and reduced odds of being diagnosed with idiopathic pulmonary fibrosis. Further, knockdown of FoxP1 in lung epithelial cells by RNA interference led to increased mRNA levels for matrix metalloproteinases 1, 2, 3 and pro-inflammatory cytokines IL-6 & IL-8, as well as reduced cell viability after exposure to cigarette smoke—all processes implicated in the pathogenesis of COPD and IPF. Conclusions Our results suggest that the protein encoded by the FoxP1 gene may protect against the development of COPD and IPF. A causal role for FoxP1 in the pathogenesis of COPD and IPF may warrant further investigation, and FoxP1 may be a novel therapeutic target for these lung disorders.

Acute myeloid leukemia with unreported translocation (x; 3) (q24; p13): A case report

“…The involvement of FOXP1 has been observed in various physiological contexts, such as the development of B‐cells, the differentiation of monocytes, and the regeneration of lung epithelia. The gene in question exhibits dual functionality in cancer, serving as both an oncogene in B‐cell lymphoma, ovarian cancer, and hepatocellular carcinoma and a tumor suppressor in T‐cell lymphoma, NSCLC (Non‐Small Cell Lung Cancer), and colorectal cancer 14–21 …”

“…The gene in question exhibits dual functionality in cancer, serving as both an oncogene in B‐cell lymphoma, ovarian cancer, and hepatocellular carcinoma and a tumor suppressor in T‐cell lymphoma, NSCLC (Non‐Small Cell Lung Cancer), and colorectal cancer. 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 …”

“…The gene in question exhibits dual functionality in cancer, serving as both an oncogene in B-cell lymphoma, ovarian cancer, and hepatocellular carcinoma and a tumor suppressor in T-cell lymphoma, NSCLC (Non-Small Cell Lung Cancer), and colorectal cancer. [14][15][16][17][18][19][20][21] Additionally, there exists supporting evidence indicating that the expression of FOXP1 in cells affected by breast cancer helps reduce the production of cytokines that attract T-cells, thereby preventing the infiltration of stated cells. 14,22 FOXP1's function in T-cells may lead to T-cell lymphoma.…”

Acute Myeloid Leukemia with Unreported Translocation (x; 3) (q24; p13): A case report

“…The gene in question exhibits dual functionality in cancer, serving as both an oncogene in B-cell lymphoma, ovarian cancer, and hepatocellular carcinoma, and a tumor suppressor in T-cell lymphoma, NSCLC (Non-Small Cell Lung Cancer), and colorectal cancer. (18)(19)(20)(21)(22)(23)(24)(25) Additionally, there exists supporting evidence indicating that the expression of FOXP1 in cells affected by breast cancer helps reduce the production of cytokines that attract T-cells, thereby preventing the infiltration of stated cells. (18,26) FOXP1's function in T-cells may lead to T-cell lymphoma.…”

Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review

“…This intricate process involves a variety of cells, proteins, and genes, such as progenitor cell states, neuroendocrine cell subtypes, fibroblast growth factor 10, FoxP1, FoxP1, THRB, EGR3, ETV1, and others. It also utilizes diverse developmental mechanisms, including IL-33/ILC2/IL-13, NOTCH, TGFB, and sonic hedgehog signaling, among others [1][2][3][4][5][6][7][8][9][10][11]. These elements are fundamental in forming structures essential for respiration, managing the critical exchange of oxygen and carbon dioxide, vital for cellular sustenance and function [12].…”