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Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of\n                    <jats:italic>p<\/jats:italic>\n                    CS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1\u03b1 and 2-\u03b1 (HIF-1\u03b1 and HIF-2\u03b1) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-\u03b1 and miR-21 in ccRCC remains unclear. Therefore, the effects of\n                    <jats:italic>p<\/jats:italic>\n                    CS on ccRCC cells were investigated for HIF-\u03b1 and miR-21 signals. Our results showed that\n                    <jats:italic>p<\/jats:italic>\n                    CS induced overexpression of HIF-1\u03b1 and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells.\n                    <jats:italic>p<\/jats:italic>\n                    CS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked\n                    <jats:italic>p<\/jats:italic>\n                    CS-induced proliferation and migration. Taken together, the present results demonstrate that\n                    <jats:italic>p<\/jats:italic>\n                    CS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21\/HIF-1\u03b1 signaling pathways.\n                  <\/jats:p>","DOI":"10.1038\/s41598-019-39646-9","type":"journal-article","created":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T06:06:43Z","timestamp":1551420403000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21\/ HIF-1\u03b1 axis signals"],"prefix":"10.1038","volume":"9","author":[{"given":"Tsai-Kun","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chyou-Wei","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ru","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-9215","authenticated-orcid":false,"given":"Ren-Jun","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Yi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Luen","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"39646_CR1","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.3892\/ol.2017.5690","volume":"13","author":"D Wang","year":"2017","unstructured":"Wang, D. et al. 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