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miR‐181b/Oncostatin m axis inhibits prostate cancer bone metastasis via modulating osteoclast differentiation
Author(s) -
Han Ziwei,
Zhan Ruisen,
Chen Shijie,
Deng Jia,
Shi Jian,
Wang Weiguo
Publication year - 2020
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29401
Subject(s) - oncostatin m , osteoclast , bone metastasis , cancer research , prostate cancer , microrna , metastasis , biology , cancer , medicine , cytokine , interleukin 6 , gene , receptor , biochemistry
The activation of osteoblasts is significantly correlated to prostate tumor bone metastasis and bone loss. Oncostatin M (OSM) could promote breast cancer metastasis to bone. However, its role and mechanism in prostate cancer bone metastasis remain unclear. MicroRNAs (miRNAs) could play important roles in cancers via post‐transcriptionally regulating target genes via binding to specific sequences in the 3′ UTR of downstream target genes. In the present study, we performed microarray profiling analyses to identify differentially‐expressed miRNAs in preosteoclast before and after osteoclast differentiation that could target OSM. miR‐181b‐5p was downregulated during Raw264.7 cells differentiation into osteoclast. By direct targeting OSM 3′ UTR, miR‐181b‐5p inhibited OSM messenger RNA expression and protein levels, subsequently decreasing IL‐6 and AREG and increasing OPG, while OSM overexpression exerted an opposing effect. More importantly, co‐culture with miR‐181b‐5p‐overexpressing differentiated Raw264.7 cells suppressed proliferation, migration, and invasion of mouse prostate cancer RM‐1 cells, while co‐culture with OSM‐overexpressing Raw264.7 cells led to opposing cellular effects. More importantly, the effects of miR‐181b‐5p on osteoclastogenic factors and RM‐1 cells could be significantly reversed by OSM overexpression. In summary, miR‐181b‐5p/OSM axis could be a viable therapeutic target for patients with surgically removed primary tumors to reduce bone metastasis and prevent bone loss.