贫氘水抑制肺癌细胞增殖的miRNAs差异表达谱分析及功能研究

体内外研究表明贫氘水作为多种癌症的辅助治疗剂可抑制癌组织生长、转移与复发，但分子机制有待阐明。课题组希望在已经开展（50~100ppm）贫氘水对多种肿瘤细胞生长有明确抑制作用和初步差异miRNAs表达谱分析的前期工作基础上，降低氘浓度对肺癌不同组织类型细胞株（肺腺癌细胞株A549、肺泡细胞癌细胞株H1650及小细胞肺癌细胞株DMS53）抑制增殖作用，进一步分析随着贫氘水（D/H）比值变化而抑制肺癌细胞增殖的过程中，miRNAs表达谱差异表达规律；候选显著差异表达miRNA-34a、miR-106a、miR-211、miR-17~92调控抑癌靶基因P53、PTEN表达的分子机制；明确miR-1291是否能通过靶击ATP酶，调控多药耐药蛋白MRP1/ABCC1的表达，增加肺癌细胞化疗的药敏性。

Some reports suggest that Deuterium depleted water(DDW) treatment, when integrated into other forms of conventional cancer therapy, can significantly decreased the growth rate of various tumor cells and also block the metastasis and recurrence in vitro and in vivo, however the underlying mechanisms remain unclear. In our previous investigation, we found that DDW with 50 ppm significantly inhibited the ability of cell proliferation cloned formation and migration. Furthermore,we preliminarily evaluated the miRNA expression profiles of A549 cell lines with or without DDW(50ppm) treatment using the Affymetrix microRNA array and we also revealed a number of potential tumor suppressor miRNAs and lots of novel miRNAs. In this study, we will address the decrease of D concerntration(5~100ppm) can intervene in the signal transduction pathways thus inducing apoptosis in lung cancer cell lines originated from different tissues(A549/H1650/DMS53). Further, we will investigate the expression pattern of potential tumor suppressor miRNAs(such as miRNA-34a、miR-106a、miR-211、miR-17~92) through potential targeting PTEN or P53. and identifying that down-regulation of ATP-binding cassette C1 protein expression in lung cancer cells after DDW(50ppm) treatment is mediated by microRNA-1291.