title: DACH1 inhibits cyclin D1 expression, cellular proliferation and tumor growth of renal cancer cells.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is a complex with diverse biological characteristics and distinct molecular signature. New target therapies to molecules that drive RCC initiation and progression have achieved promising responses in some patients, but the total effective rate is still far from satisfaction. Dachshund (DACH1) network is a key signaling pathway for kidney development and has recently been identified as a tumor suppressor in several cancer types. However, its role in renal cell carcinoma has not been fully investigated.
  
  
  METHODS
  Immunohistochemical staining for DACH1, PCNA and cyclin D1 was performed on human renal tissue microarrays and correlation with clinic-pathological characteristics was analyzed. In vitro proliferation, apoptosis and in vivo tumor growth were evaluated on human renal cancer cell lines with decitabine treatment or ectopic expression of DACH1. Downstream targets and potential molecular mechanism were investigated through western blot, immunoprecipitation and reporter gene assays.
  
  
  RESULTS
  Expression of DACH1 was significantly decreased in human renal carcinoma tissue. DACH1 protein abundance was inversely correlated with the expression of PCNA and cyclin D1, tumor grade, and TNM stage. Restoration of DACH1 function in renal clear cell cancer cells inhibited in vitro cellular proliferation, S phase progression, clone formation, and in vivo tumor growth. In mechanism, DACH1 repressed cyclin D1 transcription through association with AP-1 protein.
  
  
  CONCLUSIONS
  Our results indicated that DACH1 was a novel molecular marker of RCC and it attributed to the malignant behavior of renal cancer cells. Re-activation of DACH1 may represent a potential therapeutic strategy.
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. qianchu@tjh.tjmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. hanna102606@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Han
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. yuanxunjackson@qq.com.
authors.forename: Xun
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. 12552718@qq.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Nie
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. 958328415@qq.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. veta.chen@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology & Hepatology, Chinese PLA General Hospital, #28 Fuxing Road, Beijing, 100853, China. mzguo1@gmail.com.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. syyu@tjh.tjmu.edu.cn.
authors.forename: Shiying
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China. kmwu@tjh.tjmu.edu.cn.
authors.forename: Kongming
authors.initials: K
authors.lastname: Wu
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005136:Eye Proteins / Q000096:biosynthesis / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C530104:CCND1 protein, human; C486747:DACH1 protein, human; D005136:Eye Proteins; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D019938:Cyclin D1