miR-103与胃癌多药耐药作用机制探讨
发布时间：2018-12-15 23:55
【摘要】：目的既往研究肿瘤耐药均集中在DNA水平,而DNA又影响mRNA及蛋白质表达。但是mRNA与编码蛋白质的表达并不成比例,而非编码RNA恰好能解释两者之间的不平衡。非编码RNA即微小RNA(microRNA,miRNA),是一类内源性短链非编码小分子核糖核苷酸,长度约18~25个核糖核苷酸,是转录后基因表达调节的关键分子,参与胃癌的发生发展。本研究旨在探讨miR-103在胃癌多药耐药中作用及其分子机制。方法miRNA芯片筛选SGC7901/ADR及SGC7901细胞差异表达miRNA,应用qRT-PCR验证miR-103表达;将miR-103的拟似物及抑制物分别转染SGC7901/ADR及SGC7901细胞,MTT法检测转染前后对多柔比星敏感性变化;蛋白质印迹法检测miR-103对caveolin-1表达的影响。结果 miR-103在SGC7901/ADR细胞中表达(0.32±0.04)显著低于SGC7901细胞。miR-103拟似物转染SGC7901/ADR细胞后对多柔比星的敏感性较对照组显著提高,IC_(50)由(18.83±0.32)μg/mL下降到(4.54±0.29)μg/mL,t=1.04,P0.05;而miR-103抑制物转染SGC7901细胞后对多柔比星的敏感性显著降低,IC_(50)由(1.65±0.03)μg/mL上升到(15.27±0.26)μg/mL,t=1.25,P0.05。miR-103靶向作用于caveolin-1的3’-UTR,并在转录后水平负向调控caveolin-1表达。结论 miR-103通过靶向负调控caveolin-1表达,增加SGC7901/ADR细胞对多柔比星敏感性,从而逆转胃癌多药耐药。
[Abstract]:Objective to study the drug resistance of tumor mainly at DNA level, and DNA affects the expression of mRNA and protein. However, the expression of mRNA is not proportional to the expression of encoded protein, and the non-coding RNA can explain the imbalance between them. Noncoding RNA (microRNA,miRNA) is a class of endogenous short chain noncoding small molecular ribonucleotides with a length of about 18 ~ 25 ribonucleotides. It is a key molecule in the regulation of posttranscriptional gene expression and plays an important role in the development of gastric cancer. The purpose of this study was to investigate the role of miR-103 in multidrug resistance of gastric cancer and its molecular mechanism. Methods the differential expression of miRNA, in SGC7901/ADR and SGC7901 cells was screened by miRNA microarray and miR-103 expression was verified by qRT-PCR. MiR-103 mimicides and inhibitors were transfected into SGC7901/ADR and SGC7901 cells respectively. The sensitivity of miR-103 to doxorubicin before and after transfection was detected by MTT method. The effect of miR-103 on caveolin-1 expression was detected by Western blot. Results the expression of miR-103 in SGC7901/ADR cells (0.32 卤0.04) was significantly lower than that in SGC7901 cells, and the sensitivity to doxorubicin in SGC7901/ADR cells transfected with miR-103 mimic was significantly higher than that in control group. The IC_ (50) decreased from (18.83 卤0.32) 渭 g/mL to (4.54 卤0.29) 渭 g / m ~ (-1) P ~ (0.05); The sensitivity of miR-103 inhibitor to doxorubicin was significantly decreased after transfection of SGC7901 cells, and IC_ (50) increased from (1.65 卤0.03) 渭 g/mL to (15.27 卤0.26) 渭 g / mL ~ (-1). P0.05.miR-103 was targeted at caveolin-1 and negatively regulated the expression of caveolin-1 at post-transcriptional level. Conclusion miR-103 increases the sensitivity of SGC7901/ADR cells to doxorubicin by targeting negative regulation of caveolin-1 expression, thus reversing multidrug resistance in gastric cancer.
【作者单位】： 中国医科大学附属第一医院肿瘤内科;沈阳第五人民医院肿瘤内一科;
【基金】：国家自然科学基金(81270036;30901736;81673025) 辽宁省教育厅优秀人才支持计划(LR2014023) 辽宁省自然科学基金(2014021069)
【分类号】：R735.2
，
本文编号：2381496
[Abstract]:Objective to study the drug resistance of tumor mainly at DNA level, and DNA affects the expression of mRNA and protein. However, the expression of mRNA is not proportional to the expression of encoded protein, and the non-coding RNA can explain the imbalance between them. Noncoding RNA (microRNA,miRNA) is a class of endogenous short chain noncoding small molecular ribonucleotides with a length of about 18 ~ 25 ribonucleotides. It is a key molecule in the regulation of posttranscriptional gene expression and plays an important role in the development of gastric cancer. The purpose of this study was to investigate the role of miR-103 in multidrug resistance of gastric cancer and its molecular mechanism. Methods the differential expression of miRNA, in SGC7901/ADR and SGC7901 cells was screened by miRNA microarray and miR-103 expression was verified by qRT-PCR. MiR-103 mimicides and inhibitors were transfected into SGC7901/ADR and SGC7901 cells respectively. The sensitivity of miR-103 to doxorubicin before and after transfection was detected by MTT method. The effect of miR-103 on caveolin-1 expression was detected by Western blot. Results the expression of miR-103 in SGC7901/ADR cells (0.32 卤0.04) was significantly lower than that in SGC7901 cells, and the sensitivity to doxorubicin in SGC7901/ADR cells transfected with miR-103 mimic was significantly higher than that in control group. The IC_ (50) decreased from (18.83 卤0.32) 渭 g/mL to (4.54 卤0.29) 渭 g / m ~ (-1) P ~ (0.05); The sensitivity of miR-103 inhibitor to doxorubicin was significantly decreased after transfection of SGC7901 cells, and IC_ (50) increased from (1.65 卤0.03) 渭 g/mL to (15.27 卤0.26) 渭 g / mL ~ (-1). P0.05.miR-103 was targeted at caveolin-1 and negatively regulated the expression of caveolin-1 at post-transcriptional level. Conclusion miR-103 increases the sensitivity of SGC7901/ADR cells to doxorubicin by targeting negative regulation of caveolin-1 expression, thus reversing multidrug resistance in gastric cancer.
【作者单位】： 中国医科大学附属第一医院肿瘤内科;沈阳第五人民医院肿瘤内一科;
【基金】：国家自然科学基金(81270036;30901736;81673025) 辽宁省教育厅优秀人才支持计划(LR2014023) 辽宁省自然科学基金(2014021069)
【分类号】：R735.2
，
本文编号：2381496
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