肿瘤抑制性miRNA-135a通过靶向ELK1和ELK3癌基因抑制乳腺癌细胞增殖的研究

发布时间：2019-06-14 21:05

【摘要】：乳腺癌是一种常见的恶性疾病,miRNA是微小的非编码RNA,在癌症发展过程中可能起着重要的作用,通过靶向和沉默mRNA转录物调节基因表达。新出现的证据表明,miR-135a在乳腺癌细胞中下调,但miR-135a在乳腺癌细胞中的功能作用尚未开发。miR-135a的诱导表达显着下调ELK1和ELK3在mRNA和蛋白水平上的表达。此外,miR-135a在MCF-7和T47D细胞中的作用通过miR-135a模拟物的过表达来研究。在体外,miR-135a在乳腺癌细胞中的诱导表达抑制细胞增殖和衰老。荧光素酶活性测定显示miR-135a可以直接靶向ELK1和ELK3致癌基因的3 '非翻译区。此外,拯救实验表明miR-135a的过表达抑制细胞生长被转录因子ELK1和ELK3的过表达减弱。我们的研究表明miR-135a通过靶向ELK1和ELK3致癌基因调节乳腺癌细胞增殖,并表明miR-135a潜在地作为肿瘤抑制因子。
[Abstract]:Breast cancer is a common malignant disease. MiRNA is a small non-coding RNA, that may play an important role in the development of cancer, regulating gene expression by targeting and silencing mRNA transcripts. New evidence suggests that miR-135a is down-regulated in breast cancer cells but the functional role of miR-135a in breast cancer cells has not been developed. The induced expression of miR-135a significantly down-regulated the expression of ELK1 and ELK3 at mRNA and protein levels. In addition, the role of miR-135a in MCF-7 and T47D cells was studied by overexpression of miR-135a mimics. In vitro, the induced expression of miR-135a in breast cancer cells inhibit the proliferation and aging of breast cancer cells. Luciferase activity assay showed that miR-135a could directly target the 3 'untranslated region of ELK1 and ELK3 carcinogens. In addition, rescue experiments showed that the overexpression of miR-135a was weakened by the overexpression of transcription factors ELK1 and ELK3. Our studies have shown that miR-135a modulates the proliferation of breast cancer cells by targeting ELK1 and ELK3 carcinogenic genes, and suggests that miR-135a may potentially act as a tumor inhibitor.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R737.9

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