【摘要】：目的既往研究腫瘤耐藥均集中在DNA水平,而DNA又影響mRNA及蛋白質(zhì)表達(dá)。但是mRNA與編碼蛋白質(zhì)的表達(dá)并不成比例,而非編碼RNA恰好能解釋兩者之間的不平衡。非編碼RNA即微小RNA(microRNA,miRNA),是一類內(nèi)源性短鏈非編碼小分子核糖核苷酸,長(zhǎng)度約18~25個(gè)核糖核苷酸,是轉(zhuǎn)錄后基因表達(dá)調(diào)節(jié)的關(guān)鍵分子,參與胃癌的發(fā)生發(fā)展。本研究旨在探討miR-103在胃癌多藥耐藥中作用及其分子機(jī)制。方法miRNA芯片篩選SGC7901/ADR及SGC7901細(xì)胞差異表達(dá)miRNA,應(yīng)用qRT-PCR驗(yàn)證miR-103表達(dá);將miR-103的擬似物及抑制物分別轉(zhuǎn)染SGC7901/ADR及SGC7901細(xì)胞,MTT法檢測(cè)轉(zhuǎn)染前后對(duì)多柔比星敏感性變化;蛋白質(zhì)印跡法檢測(cè)miR-103對(duì)caveolin-1表達(dá)的影響。結(jié)果 miR-103在SGC7901/ADR細(xì)胞中表達(dá)(0.32±0.04)顯著低于SGC7901細(xì)胞。miR-103擬似物轉(zhuǎn)染SGC7901/ADR細(xì)胞后對(duì)多柔比星的敏感性較對(duì)照組顯著提高,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抑制物轉(zhuǎn)染SGC7901細(xì)胞后對(duì)多柔比星的敏感性顯著降低,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,并在轉(zhuǎn)錄后水平負(fù)向調(diào)控caveolin-1表達(dá)。結(jié)論 miR-103通過(guò)靶向負(fù)調(diào)控caveolin-1表達(dá),增加SGC7901/ADR細(xì)胞對(duì)多柔比星敏感性,從而逆轉(zhuǎn)胃癌多藥耐藥。
[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 鹵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 鹵0.32) 渭 g/mL to (4.54 鹵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 鹵0.03) 渭 g/mL to (15.27 鹵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.
【作者單位】： 中國(guó)醫(yī)科大學(xué)附屬第一醫(yī)院腫瘤內(nèi)科;沈陽(yáng)第五人民醫(yī)院腫瘤內(nèi)一科;
【基金】：國(guó)家自然科學(xué)基金(81270036;30901736;81673025) 遼寧省教育廳優(yōu)秀人才支持計(jì)劃(LR2014023) 遼寧省自然科學(xué)基金(2014021069)
【分類號(hào)】：R735.2
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本文編號(hào)：2381496