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However, whether chrysotile causes malignant mesothelioma and its molecular mechanism remain debatable. Thus, this study aimed to demonstrate the mesothelioma\u2010inducing potential of chrysotile at the mesothelial cellular level and the function of microRNA\u201028 in malignantly transformed mesothelial MeT\u20105A cells. MeT\u20105A cells malignantly transformed by a nontoxic dose of chrysotile were named Asb\u2010T, and miR\u201028 expression was downregulated in Asb\u2010T cells. Restoration of miR\u201028 expression inhibited the proliferation, migration and invasion of Asb\u2010T cells. We verified that IMPDH is a putative target of miR\u201028. The expression of IMPDH was significantly higher in Asb\u2010T MeT\u20105A cells than in control cells, whereas the opposite trend was observed with miR\u201028 overexpression. Additionally, inhibition of IMPDH had similar effects as miR\u201028 overexpression. After miR\u201028 was elevated or IMPDH was inhibited, Ras activation was reduced, and its downstream pathways (the Erk and Akt signalling pathways) were inhibited. Surprisingly, the content of miR\u201028 in the blood of mesothelioma patients was higher than that in control subjects. Overall, nontoxic doses of chrysotile can cause malignant transformation of MeT\u20105A cells. Moreover, miR\u201028 inhibits the proliferation, migration and invasion of Asb\u2010T MeT\u20105A cells, negatively regulates the expression of IMPDH through the Ras signalling pathway and may be an important therapeutic target.<\/jats:p>","DOI":"10.1002\/jat.4174","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T01:20:57Z","timestamp":1619140857000},"page":"1879-1892","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A nontoxic dose of chrysotile can malignantly transform Met\u20105A cells, in which microRNA\u201028 has inhibitory effects"],"prefix":"10.1002","volume":"41","author":[{"given":"Fangfang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuyuan","family":"Yuan","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, The Second Affiliated Hospital Zhejiang University School of Medicine  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xianhong","family":"Yin","sequence":"additional","affiliation":[{"name":"Ministry of Education Key Laboratory of Contemporary Anthropology, Department of Anthropology and Human Genetics, School of Life Sciences Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanan","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyu","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shibo","family":"Ying","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailing","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Ju","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Xiao","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianlin","family":"Lou","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8206-0570","authenticated-orcid":false,"given":"Lijin","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Public Health Hangzhou Medical College  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.12.047"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-08-731166"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8628612"},{"issue":"15","key":"e_1_2_7_5_1","first-page":"6621","article-title":"MicroRNA\u201028\u20105p regulates glioma cell proliferation, invasion and migration by targeting SphK1","volume":"23","author":"Chen H. 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