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出 处:《临床与实验病理学杂志》2016年第9期971-974,979,共5页Chinese Journal of Clinical and Experimental Pathology
基 金:安徽高等学校省级自然科学项目(KJ2013Z148)
摘 要:目的探讨信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)蛋白和miR-125a-5p在人乳腺癌组织中的表达、临床意义及其两者的相关性。方法收集150例人乳腺癌组织蜡块,应用免疫组化Max Vision法检测STAT3蛋白的表达,使用原位分子杂交技术检测miR-125a-5p的表达;使用Lipofectamine 2000介导的miRNA转染技术,荧光定量PCR技术检测转染miR-125a-5p模拟物后乳腺癌细胞MDA-MB-231的STAT3表达改变,转染miR-125a-5p抑制物后乳腺癌细胞MCF-7的STAT3表达改变;使用双荧光素报告载体技术,观察miR-125a-5p能否与STAT3的3’UTR相互作用。结果乳腺癌中STAT3蛋白表达与肿瘤大小、淋巴结转移和临床分期均呈显著正相关(P均<0.05);miR-125a-5p表达与乳腺癌肿瘤大小、淋巴结转移和临床分期均呈显著负相关(P均<0.05);乳腺癌组织中STAT3蛋白和miR-125a-5p表达呈显著负相关(r_s=-0.400,P<0.001);体外实验显示:miR-125a-5p可以显著下调乳腺癌细胞中STAT3表达,且miR-125a-5p能够与STAT3的3’UTR直接相互作用。结论乳腺癌中STAT3蛋白和miR-125a-5p表达状况与乳腺癌生长和转移等呈密切相关,STAT3是miR-125a-5p的直接靶基因,两者可能在乳腺癌发生、发展过程中发挥重要作用。Purpose To investigate the expression and clinical significance of STAT3 and miR-125a-Sp and their relationship in human breast cancer. Methods The expression of STAT3 protein and miR-125a-Sp was detected in 150 cases of breast cancer by immunohis- tochemistry of MaxVision technique and in situ hybridization, respectively. The expression of STAT3 mRNA was detected by real time- PCR after transfection of miR-125a-Sp mimic or ASO in breast cancer ceils. And luciferase reporter assay was performed to check whether the miR-125a-Sp could bind to the 3'UTR of STAT3. Results The expression of STAT3 protein was significantly and positive- ly correlated to tumor size, lymph node metastasis and clinical stage ( all P〈 0. 05 ), while the expression of miR-125a-Sp was reverse- ly correlated to tumor size, lymph node metastasis and clinical stage ( all P〈 0. 05 ). Moreover, a significant correlation was found be- tween the expression of STAT3 and miR-125a-Sp in breast cancer ( rs = - 0. 400, P 〈 0. 001 ). Real time-PCR revealed the expression of STAT3 mRNA was significantly downregulated by transfection of miR-125a-Sp mimic or ASO in breast cancer ceils in vitro. The lu- ciferase reporter assay revealed that miR-125a-Sp was directly bound to 3'UTR of STAT3. Conclusion The expression of STAT3 and miR-125a-Sp is closely correlated to tumor growth, invasion and metastasis. STAT'3 is a direct gene of miR-125a-Sp. The data suggest STAT3 and miR-125a-Sp might play important roles in the development and progression of breast cancer.
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