MiRNAs Associated Polymorphisms in the 3'UTR of MET Promote the Risk of Non-Small Cell Lung Cancer

Xiaojue Zhu; Changqing Fu; Lihua Zhang; Guoxing Xu; Shusheng Wang

MiRNAs Associated Polymorphisms in the 3'UTR of MET Promote the Risk of Non-Small Cell Lung Cancer

2015

Xiaojue Zhu | Changqing Fu | Lihua Zhang | Guoxing Xu | Shusheng Wang

Background/Aims: MET can act as an oncogene and its signaling server has essential roles in regulating tumorigenesis. Polymorphisms in MET have been reported to be associated with poor prognosis in human cancer, but an association with the risk of human non-small-cell lung cancer (NSCLC) has not been found so far. In this study rs41281081 and rs76322625, located in the 3'UTR of MET, were selected to evaluate their relationship with the risk of NSCLC among the Chinese population. Methods: A questionnaire, SNaPshot genotype assay, real time PCR assay, cell transfection and the dual luciferase reporter assay were used. Single-nucleotide polymorphisms (SNPs) of rs41281081 and rs76322625 in the 3' untranslated region (UTR) of MET was involved as a risk factor in the occurrence of NSCLC. Results: SNP rs41281081 could be regulated by miR-335 and rs76322625 could be regulated by miR-1026 to cause an up-regulation of MET in patients with NSCLC. Furthermore, the carriers of the GA and AA genotypes in rs41281081, and the CU and UU genotypes in rs76322625 presented with poor cell differentiation and large tumor size, as well as a high probability of metastasis. Conclusion: Our findings have shown that the SNPs rs41281081 and rs76322625 in MET 3ʹUTR, through disruption of the regulatory role of miR-335 and miR-1026 in MET expression, may act as promoting factors in the pathogenesis of NSCLC.

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