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Suppressing the molecular signaling pathways involved in inflammation and cancer in breast cancer cell lines MDA-MB-231 and MCF-7 by miR-590

机译:通过miR-590抑制乳腺癌细胞系MDA-MB-231和MCF-7中与炎症和癌症有关的分子信号通路

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Breast cancer is the most frequent cancer among women worldwide. Tumor immunology suggests relationships between the immune system, chronic inflammation, and cancer. The immune system may either prevent or promote carcinogenesis. Here, we evaluated molecular signaling pathways common in inflammation and cancer and detected the microRNAs which play pivotal roles in mediating these pathways. Using bioinformatics assays, signaling pathways common in inflammation and cancer, and microRNAs mediating these pathways were identified. MiR-590 was selected and cloned into the pLenti-III-eGFP vector and transfected into the breast cancer cell lines. The expression level of microRNA and the candidate genes was evaluated by real-time quantitative reverse transcription polymerase chain reaction, and the apoptosis level in transfected cells was measured by Annexin V-7AAD assay. The cell migration was tested by real-time quantitative reverse transcription polymerase chain reaction for MMP2/MMP9. The expression levels of miR-590 and the selected genes (i.e. JAK2, PI3K, MAPK1, and CREB) were measured 72?h after transfection. While miR-590 showed an over-expression, the genes were significantly down-regulated. A significant increase was observed in apoptosis level in both cell lines and MMP2/MMP9 was significantly decreased in MDA-MB-231 cells. MiR-590 was selected as a microRNA which triggers and down-regulates critical genes of signaling pathways similar in cancer and inflammation. Following the miR-590 treatment, JAK2, PI3K, MAPK1, and CREB were down-regulated and the apoptosis level was increased in breast cancer cell lines. Apparently, some microRNAs can be good candidates for novel treatments of cancer. Although miR-590 showed good results in this study, further studies are required to investigate the role of miR-590 in breast cancer therapy.
机译:乳腺癌是全世界女性中最常见的癌症。肿瘤免疫学提示免疫系统,慢性炎症和癌症之间的关系。免疫系统可以预防或促进癌变。在这里,我们评估了炎症和癌症中常见的分子信号传导途径,并检测了在介导这些途径中起关键作用的microRNA。使用生物信息学测定法,鉴定了炎症和癌症中常见的信号传导途径以及介导这些途径的microRNA。选择MiR-590并将其克隆到pLenti-III-eGFP载体中,并转染到乳腺癌细胞系中。通过实时定量逆转录聚合酶链反应评估microRNA和候选基因的表达水平,并通过膜联蛋白V-7AAD检测转染细胞的凋亡水平。通过实时定量逆转录聚合酶链反应对MMP2 / MMP9进行细胞迁移测试。转染72小时后,检测miR-590和所选基因(即JAK2,PI3K,MAPK1和CREB)的表达水平。尽管miR-590显示出过表达,但基因却明显下调。在两种细胞系中均观察到凋亡水平显着增加,并且在MDA-MB-231细胞中MMP2 / MMP9显着降低。选择了MiR-590作为microRNA,它可以触发和下调类似于癌症和炎症反应的信号通路的关键基因。在miR-590治疗后,JAK2,PI3K,MAPK1和CREB被下调,并且凋亡在乳腺癌细胞系中增加。显然,某些microRNA可能是新型癌症治疗的良好候选者。尽管miR-590在这项研究中显示出良好的结果,但仍需进一步研究以调查miR-590在乳腺癌治疗中的作用。

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