BRG1 mediates epigenetic regulation of TNFα-induced CCL2 expression in oral tongue squamous cell carcinoma cells.

Strong evidence has indicated that upregulation of chemokine (CC motif) ligand-2 (CCL2) expression and the presence of an inflammatory tumor microenvironment significantly contribute to the migratory and invasive properties of oral squamous cell carcinoma, specifically oral tongue squamous cell carcinoma (OTSCC). However, the precise epigenetic mechanism responsible for enhanced CCL2 expression in response to the inflammatory mediator tumor necrosis factor alpha (TNF-α) in OTSCC remains inadequately elucidated. We have demonstrated that the production of CCL2 can be induced by TNF-α, and this induction is mediated by the chromatin remodel protein BRG1. Through the use of a chromatin immunoprecipitation (ChIP) assay, we have found that BRG1 was involved in the recruitment of acetylated histones H3 and H4 at the CCL2 promoter, thereby activating TNF-α-induced CCL2 transcription. Furthermore, we have observed that recruitment of NF-κB p65 to the CCL2 promoter was increased following BRG1 overexpression and decreased after BRG1 knockdown in OTSCC cells. Our Re-ChIP assay has shown that BRG1 knockdown completely inhibits the recruitment of both acetylated histone H3 or H4 and NF-κB to the CCL2 promoter. In summary, the findings of our study demonstrate that BRG1 plays a significant role in mediating the production of CCL2 in OTSCC cells in response to TNF-α stimulation. This process involves the cooperative action of acetylated histone and NF-κB recruitment to the CCL2 promoter site. Our data suggest that BRG1 serves as a critical epigenetic mediator in the regulation of TNF-α-induced CCL2 transcription in OTSCC cells.

Multiple regression analysis of risk factors related to radiation pneumonitis.

BACKGROUND: Radiation pneumonitis (RP) is a severe complication of thoracic radiotherapy that may lead to dyspnea and lung fibrosis, and negatively affects patients' quality of life. AIM: To carry out multiple regression analysis on the influencing factors of radiation pneumonitis. METHODS: Records of 234 patients receiving chest radiotherapy in Huzhou Central Hospital (Huzhou, Zhejiang Province, China) from January 2018 to February 2021, and the patients were divided into either a study group or a control group based on the presence of radiation pneumonitis or not. Among them, 93 patients with radiation pneumonitis were included in the study group and 141 without radiation pneumonitis were included in the control group. General characteristics, and radiation and imaging examination data of the two groups were collected and compared. Due to the statistical significance observed, multiple regression analysis was performed on age, tumor type, chemotherapy history, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), carbon monoxide diffusion volume (DLCO), FEV1/FVC ratio, planned target area (PTV), mean lung dose (MLD), total number of radiation fields, percentage of lung tissue in total lung volume (vdose), probability of normal tissue complications (NTCP), and other factors. RESULTS: The proportions of patients aged ≥ 60 years and those with the diagnosis of lung cancer and a history of chemotherapy in the study group were higher than those in the control group (P < 0.05); FEV1, DLCO, and FEV1/FVC ratio in the study group were lower than those in the control group (P < 0.05), while PTV, MLD, total field number, vdose, and NTCP were higher than in the control group (P < 0.05). Logistic regression analysis showed that age, lung cancer diagnosis, chemotherapy history, FEV1, FEV1/FVC ratio, PTV, MLD, total number of radiation fields, vdose, and NTCP were risk factors for radiation pneumonitis. CONCLUSION: We have identified patient age, type of lung cancer, history of chemotherapy, lung function, and radiotherapy parameters as risk factors for radiation pneumonitis. Comprehensive evaluation and examination should be carried out before radiotherapy to effectively prevent radiation pneumonitis.