27‚ÄêHydroxycholesterol enhanced osteoclastogenesis in lung adenocarcinoma microenvironment
Authors: Jinglei Liu
Ming Yang
Xingkai Li
Lishan Zhang
Yanliang Lin
Ming Liu
Benhua Su
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: 27-hydroxycholesterol; NFATc1; c-Fos; miR-139; osteoclast.
Affiliations: Department of Hand and Foot SurgeryShandong Provincial Hospital Affiliated to Shandong University China, Department of Cardiothoracic SurgeryGansu Provincial Hospital of TCM, LanzhouJinan China, Department of Gastrointestinal SurgeryShandong Provincial Hospital Affiliated to Shandong UniversityJinan China, Department of Thoracic SurgeryShandong Provincial Hospital Affiliated to Shandong UniversityJinan China, Department of UltrasoundShandong Provincial Hospital Affiliated to Shandong UniversityJinan China, Department of Medical Engineering, Shandong Provincial Hospital Affiliated to Shandong UniversityJinan China, Department of Center LaboratoryShandong Provincial Hospital Affiliated to Shandong UniversityJinan China

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. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 4C. * Blue boxes: Two panels representing different cell types appear to show an overlap.  , 
 #1 Dear Elisabeth M Bik, Thank you for your reminding!. Our experimental procedure is as follows:we collected the conditioned media (CM) from A549 or H1299, and then stimulated the raw264.7 cells or raw264.7 carrying miR-139, TRAP staining was used to determine the osteoclast differentiation. Due to file designation, we wrongly uploaded the picture from the group treated with CM from A549 rather than H1299, but We did not realize that! We have provide the picture from the group of H1299. Since A549 and H1299 cells were Parallel cells, it did not affact the real results.   , 
 #1 These cells are differentiated from raw264.7 cells in both A549 cells group and H1299 cells group. , 
 Dear authors, thank you for providing the correct images. Have you already contacted the journal for a correction? ,