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AgomiR-325-3p or antagomir-325-3p were injected in tail-veins of Balb\/c mice to interfere the osteoclastogenesis and bone metastasis of CRC. Safranin O and Fast Green staining examined the changes of trabecular area and TRAP staining examined the osteoclast number in bone metastasis of CRC. Real-time PCR was conducted to test the RNA level of miR-325-3p and mRNA levels of TRAP and Cathepsin K in osteoclast precursors (OCPs). Dual-luciferase reporter system was utilized to identify the direct target of miR-325-3p. Conditioned medium from CT-26 cells was collected to stimulate the OCPs during osteoclastogenesis induced by RANKL and M-CSF in vitro. Western blot analysis was performed to examine the protein level of S100A4 in OCPs after interfered by agomiR-325-3p or antagomir-325-3p cultured in CM or not.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>miR-325-3p downregulated in OCPs in CRC microenvironment both in vivo and in vitro. By luciferase activity assay, S100A4 was the target gene of miR-325-3p and the protein level of S100A4 in OCPs upregulated in CRC microenvironment. Overexpression of miR-325-3p inhibited the osteoclastogenesis of OCPs and it can be reversed after transfection with plasmid containing S100A4. Treatment with miR-325-3p can preserve trabecular area in bone metastasis of CRC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>miR-325-3p can prevent osteoclast formation through targeting S100A4 in OCPs. Overexpression of miR-325-3p efficiently decreased the osteoclast number and attenuated bone resorption in bone metastasis of CRC.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s10020-021-00282-7","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T07:03:20Z","timestamp":1615359800000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["miR-325-3p, a novel regulator of osteoclastogenesis in osteolysis of colorectal cancer through targeting S100A4"],"prefix":"10.1186","volume":"27","author":[{"given":"Li","family":"Chengling","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Yulin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xie","family":"Xiaoyu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Xingchen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhang","family":"Sen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Ziming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5758-556X","authenticated-orcid":false,"given":"Chen","family":"Xianming","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,10]]},"reference":[{"key":"282_CR1","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1016\/j.ejca.2010.07.013","volume":"46","author":"K Boye","year":"2010","unstructured":"Boye K, Nesland JM, Sandstad B, et al. 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