title: MEIS1 inhibits clear cell renal cell carcinoma cells proliferation and in vitro invasion or migration.
abstract: Myeloid ecotropic viral integration site 1 (MEIS1) protein plays a synergistic causative role in acute myeloid leukemia (AML). However, MEIS1 has also shown to be a potential tumor suppressor in some other cancers, such as non-small-cell lung cancer (NSCLC) and prostate cancer. Although multiple roles of MEIS1 in cancer development and progression have been identified, there is an urgent demand to discover more functions of this molecule for further therapeutic design.
  
  
  
  MEIS1 was overexpressed via adenovirus vector in clear cell renal cell carcinoma (ccRCC) cells. Western blot and real-time qPCR (quantitative Polymerase Chain Reaction) was performed to examine the protein and mRNA levels of MEIS1. Cell proliferation, survival, in vitro migration and invasion were tested by MTT, colony formation, soft-agar, transwell (in vitro invasion/migration) assays, and tumor in vivo growthwas measured on nude mice model. In addition, flow-cytometry analysis was used to detect cell cycle arrest or non-apoptotic cell death of ccRCC cells induced by MEIS1.
  
  
  
  MEIS1 exhibits a decreased expression in ccRCC cell lines than that in non-tumor cell lines. MEIS1 overexpression inhibits ccRCC cells proliferation and induces G1/S arrest concomitant with marked reduction of G1/S transition regulators, Cyclin D1 and Cyclin A. Moreover, MEIS1-1 overexpression also induces non-apoptotic cell death of ccRCC cells via decreasing the levels of pro-survival regulators Survivin and BCL-2. Transwell migration assay (TMA) shows that MEIS1 attenuates in vitro invasion and migration of ccRCC cells with down-regulated epithelial-mesenchymal transition (EMT) process. Further, in nude mice model, MEIS1 inhibits the in vivo growth of Caki-1 cells.
  
  
  
  By investigating the role of MEIS1 in ccRCC cells' survival, proliferation, anchorage-independent growth, cell cycle progress, apoptosis and metastasis, in the present work, we propose that MEIS1 may play an important role in clear cell renal cell carcinoma (ccRCC) development.
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.|Department of Urology, Civil Aviation General Hospital/Civil Aviation Medical College of Peking University, Beijing, 100123, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Axiang
authors.initials: A
authors.lastname: Xu
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Yin
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China.
authors.forename: Fanglong
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Urology, Chinese PLA Medical School/Chinese PLA General Hospital, Beijing, 100853, People's Republic of China. jpgao@163.com.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D051379:Mice; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin
keywords: Clear cell renal cell carcinoma; MEIS1; Proliferation; in vitro invasion or migration