title: Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.
abstract: OBJECTIVE
  This study was implemented to investigate the associations between SNP in mature microRNA (miRNA) sequence and lung cancer prognosis and to verify the function of those SNP.
  
  
  METHODS
  Eight SNPs (rs3746444T>C in hsa-mir-499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293, rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) were analyzed in a southern Chinese population with 576 patients with lung cancer, and the significant results were validated in two additional cohorts of 346 and 368 patients, respectively. A series of experiments were performed to evaluate the relevancies of those potentially functional SNPs.
  
  
  RESULTS
  We found that the microRNA-499 rs3746444T>C polymorphism exhibited a consistently poor prognosis for patients with lung cancer in the discovery set [HR, 1.24; 95% confidence interval (CI), 1.02-1.49; P = 0.028], in the validation set I (HR, 1.31; 95% CI, 1.01-1.71; P = 0.048) and in the validation set II (HR, 1.45; 95% CI, 1.12-1.86; P = 0.004). The adverse effect of CT/CC variants was more remarkable in patients receiving platinum-based chemotherapy. Further functional assays demonstrated that the rs3746444C variant allele influences the expression of several cancer-related genes and affects lung cancer cells' proliferation and tumor growth in vivo and in vitro via the cisplatinum resistance.
  
  
  CONCLUSIONS
  Our findings suggested that the rs3746444T>C polymorphism in mature miR-499 sequence could contribute to poor prognosis by modulating cancer-related genes' expression and thus involve tumorigenesis and anti-chemotherapy, which may be a useful biomarker to predict lung cancer patients' prognosis.
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Fuman
authors.initials: F
authors.lastname: Qiu
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Ling
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Yang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Fang
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China. Dongguan Taiping People Hospital, Dongguan, PR China.
authors.forename: Chenli
authors.initials: C
authors.lastname: Xie
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Genetics, Medical College of Soochow University, Suzhou, PR China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, Guangzhou, PR China. jcLu@gzhmu.edu.cn.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
mesh_terms: D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017671:Platinum Compounds / Q000627:therapeutic use; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D017671:Platinum Compounds