The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer
The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer
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DOI：
10.1007/s11033-014-3793-2
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发表时间：
2015-02-01
影响因子：
2.8
通讯作者：
Oztuzcu, Serdar
中科院分区：
文献类型：
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作者：
Ergun, Sercan;Ulasli, Mustafa;Oztuzcu, Serdar
MicroRNAs可以调节许多生物功能。MIR-122-5P通过不同的分子途径发挥肿瘤抑制作用。此外，我们的第二次打击，ADAM10，被miR-122-5p靶向，是导致曲妥珠单抗不能与HER2受体结合的HER2脱落的主要决定因素。因此，我们对ADAM10表达和miR-122-5p的分析是了解乳腺癌发生的分子机制的一个很好的切入点。在我们的研究中，我们研究了71例乳腺癌患者miR-122-5p及其靶向ADAM10的表达谱。用免疫组织化学方法分析ER、PR和HER2基因产物对肿瘤的分类。评价miR-122-5p和ADAM10的表达数据和免疫组织化学结果，以评价miR-122-5p与ADAM10的关系。ADAM10在肿瘤中的表达高于正常组织，而miR-122-5p在肿瘤中的表达低于正常组织。HER2+患者的表达模式与总体结果相反。这可以解释为miR-122-5p的表达增加，特别是在HER2+癌细胞中，抑制了ADAM10在HER2受体上的脱落活性。然而，肿瘤抑制基因miR-122-5p的表达增加并不足以抑制ADAM10。总之，我们可以认为miR-122-5p可能是ADAM10和曲妥珠单抗耐药的潜在调节因子。因为如果我们增加miR-122-5p的活性，同时给予曲妥珠单抗，那么HER2+乳腺癌细胞可能会通过抑制ADAM10在HER2受体上的脱落活性来克服曲妥珠单抗的耐药性，从而提高曲妥珠单抗的效率。
MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.