title: Osteoclastic miR-214 targets TRAF3 to contribute to osteolytic bone metastasis of breast cancer.
abstract: The role of osteoclastic miRNAs in regulating osteolytic bone metastasis (OBM) of breast cancer is still underexplored. Here, we examined the expression profiles of osteoclastogenic miRNAs in human bone specimens and identified that miR-214-3p was significantly upregulated in breast cancer patients with OBM. Consistently, we found increased miR-214-3p within osteoclasts, which was associated with the elevated bone resorption, during the development of OBM in human breast cancer xenografted nude mice (BCX). Furthermore, genetic ablation of osteoclastic miR-214-3p in nude mice prevent the development of OBM. Conditioned medium from MDA-MB-231 cells dramatically stimulated miR-214-3p expression to promote osteoclast differentiation. Mechanistically, a series of in vitro study showed that miR-214-3p directly targeted Traf3 to promote osteoclast activity and bone-resorbing activity. In addition, osteoclast-specific miR-214-3p knock-in mice showed remarkably increased bone resorption when compared to the littermate controls, which was attenuated after osteoclast-targeted treatment with Traf3 3'UTR-containing plasmid. In BCX nude mice, osteoclast-targeted antagomir-214-3p delivery could recover the TRAF3 protein expression and attenuate the development of OBM, respectively. Collectively, inhibition of osteoclastic miR-214-3p may be a potential therapeutic strategy for breast cancer patients with OBM. Meanwhile, the intraosseous TRAF3 could be a promising biomarker for evaluation of the treatment response of antagomir-214-3p.
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery in Institute of Integrated Bioinfomedicine &Translational Science, HKBU Institute of Research and Continuing Education, Shenzhen, China.
authors.forename: Defang
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery in Institute of Integrated Bioinfomedicine &Translational Science, HKBU Institute of Research and Continuing Education, Shenzhen, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Dang
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: He
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery in Institute of Integrated Bioinfomedicine &Translational Science, HKBU Institute of Research and Continuing Education, Shenzhen, China.
authors.forename: Hilda Y S
authors.initials: HY
authors.lastname: Cheung
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Biao
authors.initials: B
authors.lastname: Liu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Fangfei
authors.initials: F
authors.lastname: Li
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Luyao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Atik Badshah
authors.initials: AB
authors.lastname: Shaikh
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.
authors.forename: Changwei
authors.initials: C
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen People's Hospital, Ji Nan University Second College of Medicine, Shenzhen, China.
authors.forename: Songlin
authors.initials: S
authors.lastname: Peng
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Zongkang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Bao-Ting
authors.initials: BT
authors.lastname: Zhang
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Bao'an Hospital Affiliated to Southern Medical University &Shenzhen 8th People Hospital, Shenzhen, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Guanghua Integrtive Medicine Hospital/Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Lianbo
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery in Institute of Integrated Bioinfomedicine &Translational Science, HKBU Institute of Research and Continuing Education, Shenzhen, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.|Guanghua Integrtive Medicine Hospital/Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Aiping
authors.initials: A
authors.lastname: Lu
authors.affiliation: Institute for Advancing Translational Medicine in Bone &Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.|Institute of Precision Medicine and Innovative Drug Discovery, Hong Kong Baptist University, Hong Kong SAR, China.|Shenzhen Lab of Combinatorial Compounds and Targeted Drug Delivery in Institute of Integrated Bioinfomedicine &Translational Science, HKBU Institute of Research and Continuing Education, Shenzhen, China.|Shum Yiu Foon Shum Bik Chuen Memorial Centre for Cancer and Inflammation Research, Hong Kong Baptist University, Hong Kong SAR, China.|Guanghua Integrtive Medicine Hospital/Shanghai University of Traditional Chinese Medicine, Shanghai, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001859:Bone Neoplasms / Q000473:pathology / Q000556:secondary*; D001862:Bone Resorption / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D005260:Female; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis / Q000378:metabolism / Q000473:pathology*; D000067996:RAW 264.7 Cells; D048008:TNF Receptor-Associated Factor 3 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D008081:Liposomes; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D048008:TNF Receptor-Associated Factor 3