title: KRT6 interacting with notch1 contributes to progression of renal cell carcinoma, and aliskiren inhibits renal carcinoma cell lines proliferation in vitro.
abstract: Notch signaling is a conserved and widely expressed signaling pathway, which mediates various physiological processes including tumorigenesis. This study aims to explore the potential role and mechanism of notch1 interacting with KRT6B in the progression of RCC. The results indicated that the mRNA and protein expression of notch1 and KRT6 were significantly increased in tumor tissues, and highly positive correlation existed between notch1 and KRT6. Moreover, the patients with high notch1 expression had a significantly poorer prognosis than those of low expression patients. In vitro, KRT6 loss-of-function could inhibit the expression of notch1 and induce renal carcinoma cell death. Eventually, we found that renin inhibitor, aliskiren, could inhibit cell proliferation and decrease the expression of notch1 and KRT6 as well as regulate apoptosis-related protein expression in 786-O and ACHN renal carcinoma cell lines. These results suggested that the upregulation of notch1 and KRT6B might be involved in the development, progression and prognosis of human RCC, and aliskiren could suppress renal carcinoma cell proliferation, at least partially, through downregulation the expression of notch1 and KRT6.
authors.affiliation: Department of Nephrology, Shanghai Seventh People's Hospital Shanghai 200137, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Pharmacy, Shanghai Seventh People's Hospital Shanghai 200137, China.
authors.forename: Li-Chao
authors.initials: LC
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Shanghai Seventh People's Hospital Shanghai 200137, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Nephrology, Shanghai Seventh People's Hospital Shanghai 200137, China.
authors.forename: Jian-Rao
authors.initials: JR
authors.lastname: Lu
authors.affiliation: Department of Nephrology, Shanghai Seventh People's Hospital Shanghai 200137, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Jin
mesh_terms: D000577:Amides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D018450:Disease Progression; D005260:Female; D005650:Fumarates / Q000494:pharmacology*; D020868:Gene Silencing; D006801:Humans; D053553:Keratin-6 / Q000378:metabolism*; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D034741:RNA, Small Interfering; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation
chemical_list: D000577:Amides; D005650:Fumarates; D053553:Keratin-6; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; C446481:aliskiren
keywords: KRT6; Renal carcinoma; aliskiren; notch1