title: A variant in 3'-untranslated region of KRAS compromises its interaction with hsa-let-7g and contributes to the development of lung cancer in patients with COPD.
abstract: OBJECTIVE
  The objective of the present study was to explore the molecular mechanism by which a single nucleotide polymorphism (rs712) interferes with interaction between 3'-untranslated region (3'-UTR) of KRAS and let-7g, and its association with development of lung cancer in the patients with COPD.
  
  
  METHODS
  In this study, we confirmed that KRAS is a target of let-7g in lung cancer cells, and that introduction of rs712 minor allele into 3'-UTR significantly compromised the miRNA/mRNA interaction by using a luciferase reporter system. Additionally, a total of 35 lung tissue samples were obtained (TT:17, TG:12, GG:6), and let-7g and KRAS expression levels were determined.
  
  
  RESULTS
  We showed that let-7g level was similar between groups, and the concentration of KRAS in GG genotype group was significantly higher than in TT or GT genotype group. Meanwhile, we found COPD patients with GG genotype had significantly higher risk for lung cancer (odds ratio OR =6.83, P=0.0081), compared with TT and GT genotypes.
  
  
  CONCLUSIONS
  Our study demonstrated that KRAS 3'-UTR rs712 polymorphism interfered with miRNA/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD.
authors: The Respiratory Department, Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
authors: Hua
authors: H
authors: Hu
authors: The Respiratory Department, Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
authors: Linlin
authors: L
authors: Zhang
authors: The Respiratory Department, Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
authors: Geling
authors: G
authors: Teng
authors: The Respiratory Department, Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
authors: Yanhua
authors: Y
authors: Wu
authors: The Clinical Laboratory of Shandong Provincial Chest Hospital, Jinan, Shandong, People's Republic of China.
authors: Ying
authors: Y
authors: Chen
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D016009:Chi-Square Distribution; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014162:Transfection
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; D035683:MicroRNAs; D012333:RNA, Messenger; C487931:mirnlet7 microRNA, human; D008156:Luciferases; D016283:Proto-Oncogene Proteins p21(ras)
keywords: KRAS; chronic obstructive pulmonary disease; let-7g; lung cancer; single nucleotide polymorphism