Abstract
MiRNAs have been focused for their wide range of biological regulatory functions. Previous studies have suggested that individual miRNAs could influence tumorigenesis through their regulation of specific proto-oncogenes and tumor suppressor genes. This study was implemented to investigate the associations between SNPs in mature microRNAs (miRNAs) and development of lung cancer in a two-stage, case-control study, followed by some functional validations. First, 11 SNPs were analyzed in a case-control study of lung cancer, and the significant results were validated in an additional population. Our results showed that rs3746444 in mir-499 (allele C vs T: OR = 1.33; 95% CI = 1.15−1.54; P = 1.2 × 10−4) and rs4919510 in mir-608 (allele G vs C: OR = 1.27; 95% CI= 1.13−1.43; P = 5.1 × 10−5) were significantly associated with increased risk of lung cancer. Rs3746444 in mir-499 was also significantly associated with poor survival of lung cancer (HR, 1.35; 95% CI, 1.15–1.58; P = 0.0002). The expression levels of mir-499 and mir-608 were significantly lower than those of adjacent normal tissues (P < 0.0005), and the carriers of minor alleles have lower expression levels of mir-499 and mir-608 than those of major alleles (P < 0.001). These findings indicated that rs3746444 in mir-499 and rs4919510 in mir-608 might play a substantial role in the susceptibility to lung cancer.
Highlights
Lung cancer is the most common cancer in terms of both incidence and mortality worldwide, accounting for 13% of the total cancer cases and 18% of the cancer deaths [1,2,3]
Our results showed that rs3746444 in mir-499 and rs4919510 in mir-608 were significantly associated with increased risk of lung cancer
1The Cox regression analysis was adjusted for age, gender, smoking, stage, surgery, chemotherapy, and radiotherapy status. In this two-stage, case-control study with a total of 1,200 lung cancer cases and 1,200 controls from Han Chinese population, we investigated the associations of 11 common SNPs located in miRNAs’ mature sequences with risk of lung cancer
Summary
Lung cancer is the most common cancer in terms of both incidence and mortality worldwide, accounting for 13% of the total cancer cases and 18% of the cancer deaths [1,2,3]. MicroRNAs (miRNAs) are small (approximately 18-24 nt), noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis [9]. They could influence tumorigenesis through their regulation of specific protooncogenes and tumor suppressor genes [10,11,12,13,14,15,16]. Polymorphisms in the miRNA pathway are emerging as powerful tools to study the cancer biology and have the potential to be used in cancer prognosis and diagnosis, especially for the genetic variants located in the mature miRNAs sequence, which could affect transcription of miRNA primary transcripts and processing of miRNA precursors [19, 20]
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