title: A functional variant in miR-155 regulation region contributes to lung cancer risk and survival.
abstract: Emerging evidence suggested that upregulation of miR-155 could serve as a promising marker for the diagnosis and prognosis of non-small cell lung cancer (NSCLC). In the present study, we genotyped rs767649 (A > T) located in miR-155 regulation region in 1341 cases and 1982 controls, and analyzed the associations of rs767649 with NSCLC risk and survival. Consequently, rs767649 exhibited the significant associations with the risk (adjusted OR = 1.12, 95% CI = 1.01-1.24, P = 0.031) and prognosis of NSCLC (adjusted HR = 1.17, 95% CI = 1.03-1.32, P = 0.014). Meanwhile, rs767649 specifically interacted with radio-chemotherapy (P(int) = 0.013), and patients with both the rs767649-TT genotype and radio-chemotherapy had the highest hazard ratio (adjusted HR = 1.65, 95% CI = 1.26-2.16, P < 0.001). Furthermore, using functional assays and The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma (LUAD) dataset, we found that rs767649 variant allele could increase the transcriptional activity of miR-155, which in turn facilitated tumor growth and metastasis by inhibiting HBP1, TJP1, SMAD5 and PRKAR1A expression. Our findings suggested that rs767649 A > T might contribute to the increased risk and poor prognosis of NSCLC, highlighting the importance of rs767649 in the prevention and therapy of NSCLC.
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Xie
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Qin
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Yayun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Caiwang
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ningbin
authors.initials: N
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhu
authors.affiliation: The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Shuangshuang
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Guangfu
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Shen
authors.affiliation: Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.|Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Hu
mesh_terms: D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012306:Risk; D012307:Risk Factors; D014162:Transfection
chemical_list: C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: genetic susceptibility; miR-155; non-small cell lung cancer; prognosis