27-Hydroxycholesterol enhanced osteoclastogenesis in lung adenocarcinoma microenvironment
作者
Zhang, LS;Liu, M;Liu, JL;Li, XK;Yang, M;Su, BH;Lin, YL
作者单位
[Lin, Yanliang] Shandong Univ, Shandong Prov Hosp, Dept Ctr Lab, 544 Jingsi Rd, Jinan 250021, Shandong, Peoples R China.;-;[Zhang, Lishan] Shandong Univ, Shandong Prov Hosp, Dept Hand & Foot Surg, Jinan, Shandong, Peoples R China.;-;[Liu, Ming] Gansu Prov Hosp TCM, Dept Cardiothorac Surg, Lanzhou, Gansu, Peoples R China.;-;[Liu, Jinglei] Shandong Univ, Shandong Prov Hosp, Dept Gastrointestinal Surg, Jinan, Shandong, Peoples R China.;-;[Li, Xingkai] Shandong Univ, Shandong Prov Hosp, Dept Thorac Surg, Jinan, Shandong, Peoples R China.;-;[Yang, Ming] Shandong Univ, Shandong Prov Hosp, Dept Ultrasound, Jinan, Shandong, Peoples R China.;-;[Su, Benhua] Shandong Univ, Shandong Prov Hosp, Dept Med Engn, 324 Jingwu Rd, Jinan 250021, Shandong, Peoples R China.
摘要
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.
关键词
NECROSIS-FACTOR-ALPHA; BONE METASTASIS; KAPPA-B; CANCER; CELLS; EXPRESSION; TRANSCRIPTION; OSTEOBLASTS; CONTRIBUTES; SUPPRESSION
基本信息
