title: The candidate oncogene (MCRS1) promotes the growth of human lung cancer cells via the miR-155-Rb1 pathway.
abstract: BACKGROUND
  Microspherule protein 1 (MCRS1) is a candidate oncogene and participates in various cellular processes, including growth, migration, senescence and transformation. MCRS1 is overexpressed in non-small cell lung cancer (NSCLC) and promotes the growth of cancer cells. However, the mechanisms driving these processes are not fully understood.
  
  
  METHODS
  Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in cell lines. Cell proliferation assays and animal experiments were respectively performed to evaluate the growth of NSCLC cells in vitro and in vivo. Microarray analysis was carried out for mRNA profiling. Luciferase reporter assay and microRNA (miRNA) transfection were used to investigate the interaction between miRNA and gene.
  
  
  RESULTS
  Stably knocking down MCRS1 expression inhibited the proliferation of NSCLC cells in vitro and in vivo. By comparing the mRNA expression profiles of NSCLC cells with or without MCRS1 silencing, we found that MCRS1 regulated expressions of various genes related to cell proliferation, including Rb1, TP53, cell cycle-related genes, MYC, E2F2, PCNA, and Ki67. However, MCRS1 did not directly bind to these differentially expressed genes. Here, we confirmed that Rb1, an important tumor suppression gene (TSG), is a direct target of miR-155 which is directly up-regulated by MCRS1. Furthermore, the level of Rb1 expression in NSCLC tissues was inversely correlated with those of miR-155 and MCRS1, and MCRS1 regulated expression of Rb1 via miR-155. Additionally, we found that the DNA copy number of the MCRS1 gene played a role in MCRS1 overexpression in NSCLCs.
  
  
  CONCLUSIONS
  MCRS1 overexpression induced NSCLC proliferation through the miR-155-Rb1 pathway and DNA copy-number amplification is one of the mechanisms underlying MCRS1 overexpression in NSCLC. Moreover, we put forward the hypothesis that there are regulatory relationships between oncogenes and TSGs apart from the functional synergy of both; the oncogene-miRNA-TSG networks are one of mechanisms among the regulatory relationships; the regulatory relationships and the networks might play active roles in the development and progression of cancer.
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. L-M-X101@163.com.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China. L-M-X101@163.com.
authors.forename: Minxia
authors.initials: M
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. zhoukecheng1988@gmail.com.|Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, China. zhoukecheng1988@gmail.com.
authors.forename: Kecheng
authors.initials: K
authors.lastname: Zhou
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The Third Affiliated Hospital of Kunming Medical University (Yunnan Tumor Hospital), Kunming, China. huangych2001@aliyun.com.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Laboratory of Molecular and Experimental Pathology, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China. caoy@mail.kiz.ac.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C113292:MCRS1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D016160:Retinoblastoma Protein