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Sequence Variation in Mature MicroRNA-499 Confers Unfavorable Prognosis of Lung Cancer Patients Treated with Platinum-Based Chemotherapy.

Qiu, Fuman; Yang, Lei; Ling, Xiaoxuan; Yang, Rongrong; Yang, Xiaorong; Zhang, Lisha; Fang, Wenxiang; Xie, Chenli; Huang, Dongsheng; Zhou, Yifeng; Lu, Jiachun.
Clin Cancer Res; 21(7): 1602-13, 2015 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-25614447

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

CONCLUSION:

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.
Selo DaSilva