2. Academic Validation
  3. The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1α axis signals

The uremic toxin p-cresyl sulfate induces proliferation and migration of clear cell renal cell carcinoma via microRNA-21/ HIF-1α axis signals

  • Sci Rep. 2019 Mar 1;9(1):3207. doi: 10.1038/s41598-019-39646-9.
Tsai-Kun Wu 1 2,  Chyou-Wei Wei 3 4,  Ying-Ru Pan 2 3,  Ren-Jun Hsu 5,  Chung-Yi Wu 1 6,  Yung-Luen Yu 7 8 9 10 11
Affiliations

Affiliations

  • 1 The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, 404, Taiwan.
  • 2 Division of Renal Medicine, Tungs' Taichung Metroharbor Hospital, Taichung, 435, Taiwan.
  • 3 Deparment of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung, 433, Taiwan.
  • 4 Department of Nursing, Hungkuang University, Taichung, 433, Taiwan.
  • 5 Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, 114, Taiwan.
  • 6 The Genomics Research Center, Academia Sinica, Taipei, 115, Taiwan.
  • 7 The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung, 404, Taiwan. ylyu@mail.cmu.edu.tw.
  • 8 Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan. ylyu@mail.cmu.edu.tw.
  • 9 Drug Development Center, China Medical University, Taichung, 404, Taiwan. ylyu@mail.cmu.edu.tw.
  • 10 Center for Molecular Medicine, China Medical University Hospital, Taichung, 404, Taiwan. ylyu@mail.cmu.edu.tw.
  • 11 Department of Biotechnology, Asia University, Taichung, 413, Taiwan. ylyu@mail.cmu.edu.tw.
PMID: 30824757 DOI: 10.1038/s41598-019-39646-9
Abstract

p-Cresyl sulfate (pCS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal Cancer. However, the effect of pCS 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-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of pCS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that pCS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. pCS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked pCS-induced proliferation and migration. Taken together, the present results demonstrate that pCS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.

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