A functional variant in miR-155 regulation region contributes to lung cancer risk and survival
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Kaipeng Xie1,2,*, Hongxia Ma1,2,*, Cheng Liang1,2,*, Cheng Wang1,2, Na Qin1,2, Wei Shen1,2, Yayun Gu1,2, Caiwang Yan1,2, Kai Zhang1,2, Ningbin Dai1,2, Meng Zhu1,2, Shuangshuang Wu3, Hui Wang1,2, Juncheng Dai1,2, Guangfu Jin1,2, Hongbing Shen1,2, Zhibin Hu1,2
1Department of Epidemiology and Biostatistics, Collaborative Innovation Center of Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, China
2Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, School of Public Health, Nanjing Medical University, Nanjing, China
3The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
*These authors have contributed equally to this work
Zhibin Hu, e-mail: [email protected]
Keywords: non-small cell lung cancer, genetic susceptibility, prognosis, miR-155
Received: July 11, 2015 Accepted: October 16, 2015 Published: October 29, 2015
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 (Pint = 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.
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