VEGF和KRAS是miR-206在三阴性乳腺癌中调节的潜在靶点

Shaymaa E. El Feky, Fawziya A. R. Ibrahim, A. Nassar, N. A. E. Moneim, S. A. Ebeid, Mohammad Ahmad, Sanaa Shawky, Mohammad M. Nasef
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摘要

三阴性是一种以缺乏激素受体(ER、PR和Her2/neu)表达为特征的乳腺癌亚型。由于治疗方案有限,寻找新的治疗靶点仍在继续。本研究的目的是评估miR-206、VEGF和KRAS在TNBC和非TNBC组织细胞系中的差异表达,并评估miR-206对关键致癌靶点VEGF和KRAS的调节作用。采用real - time PCR定量检测乳腺癌石蜡包埋组织及癌旁组织、MDA-MB-231和MCF-7细胞系中miR-206、VEGF和KRAS的表达。用不同浓度的miR-206模拟物转染细胞系,并使用MTT法评估其生存能力。我们的研究结果表明,miR-206在癌变组织中比在非癌变组织中显著下调,在TNBC中比在非TNBC组织中下调更为明显。与非TNBC相比,TNBC中VEGF和KRAS的表达显著上调,且其表达与miR-206表达呈负相关。用miR-206模拟物转染TNBC和非TNBC细胞系导致细胞活力的剂量依赖性降低,以及VEGF和KRAS表达的显著降低。总之,基于我们基于人体组织和细胞系的联合研究,我们可以提出VEGF和KRAS可能是miR-206介导的调控的潜在靶点,并且miR-206靶向它们可能是TNBC的高效治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
VEGF and KRAS are Potential Targets of miR-206 Modulation in Triple Negative Breast Cancer
Triple negative is a subtype of breast cancer characterized by lack of expression of hormone receptors (ER, PR and Her2/neu). Due to the limited treatment options, the search for novel treatment targets continues. The aim of this study was to assess the differential expression of miR-206, VEGF and KRAS in TNBC and non-TNBC tissues and cell lines and to evaluate the modulatory effect of miR-206 on the key oncogenic targets VEGF and KRAS. The expression of miR-206, VEGF and KRAS was quantified using real time PCR in both paraffin embedded breast cancer and adjacent tissues as well as in MDA-MB-231 and MCF-7 cell lines. Cell lines were transfected with different concentrations of miR-206 mimic and their viability were assessed using MTT assay. Our results indicated that miR-206 was significantly downregulated in cancerous compared to non-cancerous tissues with a more pronounced downregulation in TNBC than non-TNBC tissues. VEGF and KRAS were significantly upregulated in TNBC compared to non-TNBC and their expression was negatively correlated to miR-206 expression. Transfection of TNBC and non-TNBC cell lines with miR-206 mimic resulted in a dose dependent reduction in cell viability as well as a significant reduction in VEGF and KRAS expression. In conclusion, based on our combined human tissues and cell line-based investigations we can suggest that VEGF and KRAS may be potential targets for miR-206-mediated regulation and that their targeting by miR-206 can be a highly efficient therapeutic strategy in TNBC.
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