title: MicroRNA-26a/b regulate DNA replication licensing, tumorigenesis, and prognosis by targeting CDC6 in lung cancer.
abstract: Cancer is characterized by mutations, genome rearrangements, epigenetic changes, and altered gene expression that enhance cell proliferation, invasion, and metastasis. To accommodate deregulated cellular proliferation, many DNA replication-initiation proteins are overexpressed in human cancers. However, the mechanism that represses the expression of these proteins in normal cells and the cellular changes that result in their overexpression are largely unknown. One possible mechanism is through miRNA expression differences. Here, it is demonstrated that miR26a and miR26b inhibit replication licensing and the proliferation, migration, and invasion of lung cancer cells by targeting CDC6. Importantly, miR26a/b expression is significantly decreased in human lung cancer tissue specimens compared with the paired adjacent normal tissues, and miR26a/b downregulation and the consequential upregulation of CDC6 are associated with poorer prognosis of patients with lung cancer. These results indicate that miR26a/b repress replication licensing and tumorigenesis by targeting CDC6.
  
  
  CONCLUSIONS
  The current study suggests that miR26a, miR26b, and CDC6 and factors regulating their expression represent potential cancer diagnostic and prognostic markers as well as anticancer targets.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Dakai
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Guangzhou HKUST Fok Ying Tung Research Institute, Guangzhou, China. Division of Life Science and Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Guangzhou HKUST Fok Ying Tung Research Institute, Guangzhou, China. Division of Life Science and Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong, China.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Weixuan
authors.initials: W
authors.lastname: Lin
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.
authors.forename: Jiangfen
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Guangzhou HKUST Fok Ying Tung Research Institute, Guangzhou, China. Division of Life Science and Center for Cancer Research, Hong Kong University of Science and Technology, Hong Kong, China. bccliang@ust.hk hejx@vip.163.com.
authors.forename: Chun
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China. bccliang@ust.hk hejx@vip.163.com.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000368:Aged; D001483:Base Sequence; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004261:DNA Replication; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000378:metabolism*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; C103706:CDC6 protein, human; C528163:MIRN26 microRNA, human