27‐Hydroxycholesterol enhanced osteoclastogenesis in lung adenocarcinoma microenvironment

Abstract

27‐Hydroxycholesterol (27‐HC) has been implicated in the pathological process of estrogen receptor positive breast cancer. However, the role of 27‐HC in lung adenocarcinoma is still unclear. Because bone metastasis is a main reason for the high mortality of lung adenocarcinoma, this study aimed to investigate the effect of 27‐HC on osteoclastogenesis in lung adenocarcinoma microenvironment. The results showed that the conditioned media (CM) from lung adenocarcinoma cells cocultured with macrophages promoted osteoclast differentiation, which was enhanced by 27‐HC. Further investigation showed that CM inhibited miR‐139 expression and promoted c‐Fos expression. Luciferase reporter assay identified c‐Fos as a direct target of miR‐139. CM also induced the expression and nuclear translocation of NFATc1 and STAT3 phosphorylation, which was enlarged by 27‐HC but was attenuated by miR‐139. Coimmunoprecipitation assay demonstrated that 27‐HC increased the interaction between NFATc1 and phosphorylated STAT3, which was restricted by miR‐139. Chromatin immunoprecipitation assay showed that pSTAT3 could bind to the promoter of c‐Fos, c‐Fos could bind to the promoter of NFATc1, and both pSTAT3 and NFATc1 could bind to the promoter of Oscar, which were enlarged by 27‐HC but were blocked by miR‐139. Knockdown of c‐Fos mimicked the effect of miR‐139. These results suggested that CM, especially containing 27‐HC, promoted osteoclastogenesis by inhibiting miR‐139 expression and activating the STAT3/c‐Fos/NFATc1 pathway.

Incidence, prognostic factors, and a nomogram of lung cancer with bone metastasis at initial diagnosis: a population-based study

“…The study of lung cancer and its prognosis has always been a focus of research (18)(19)(20). Nowadays, with the development of basic research (21)(22)(23) and the emergence of new detection techniques (24) and indicators (25)(26)(27), the diagnosis and treatment of lung cancer are improving (28)(29)(30). Another item worth mentioning is the emergence of lung cancer screening programs.…”

Increased Plasma Level of 24S-Hydroxycholesterol and Polymorphism of CYP46A1 SNP (rs754203) Are Associated With Mild Cognitive Impairment in Patients With Type 2 Diabetes

“…However, its effects within the brain remain unclear, and it is not expected to contribute to the pool of cholesterol in the brain ( Hughes et al, 2013 ). Other studies have reported that it is also related to many non-neurological diseases, such as breast cancer, prostate cancer, lung adenocarcinoma, and COVID-19 ( Marwarha et al, 2017 ; Zhang et al, 2019 ; Marcello et al, 2020 ). Therefore, compared with 24-OHC, 27-OHC seems to lack a certain specificity for cognitive disorders.…”

Water‐soluble fraction of particulate matter <2.5 μm promoted lung epithelia cells apoptosis by regulating the expression of caveolin‐1 and Krüppel‐like factor 5

“…The ChIP assay was performed as described previously (Zhang et al, 2019). Briefly, treated cells were incubated with 1% fresh formaldehyde to crosslink for 10 min at room temperature, and were subsequently treated with 0.125 M glycine for 5 min.…”