miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: Significance of their regulation

miR-21 and its target gene CCL20 are both highly overexpressed in the microenvironment of colorectal tumors: Significance of their regulation
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DOI:
10.3892/or.2013.2580
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发表时间:
2013-09-01
期刊:
影响因子:
4.2
通讯作者:
Glanemann, Matthias
Glanemann, Matthias
中科院分区:
医学3区
文献类型:
--
作者:
Vicinus, Benjamin;Rubie, Claudia;Glanemann, Matthias

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最近,我们报道了结直肠癌(CRC)细胞系中 miR-21 与其确定的趋化因子靶点 CCL20 之间的功能相互作用。在这里,我们研究了在细胞水平上是否允许这种功能相互作用,这需要在同一细胞中表达负相关以及 miR-21 和 CCL20 的共表达。使用 qPCR 进行表达谱分析,并应用 ELISA、原位杂交和免疫组织化学来展示其细胞定位。我们证明 miR-21 和 CCL20 在 CRC 组织中均显着上调;因此,没有表现出逆向表达模式。这提供了miR-21和CCL20可能不在同一细胞中表达的初步线索。此外,我们在细胞水平上发现 miR-21 表达主要在肿瘤相关成纤维细胞等基质细胞中,在巨噬细胞和淋巴细胞等免疫细胞中也有少量表达。同样,CCL20 表达主要在肿瘤浸润免疫细胞中检测到。因此,研究 miR-21 及其靶标 CCL20 的细胞定位表明,这两种分子主要在 CRC 肿瘤的微环境中表达。
Recently, we reported a functional interaction between miR-21 and its identified chemokine target CCL20 in colorectal cancer (CRC) cell lines. Here, we investigated whether such functional interactions are permitted at the cellular level which would require an inverse correlation of expression and also co-expression of miR-21 and CCL20 in the same cell. Expression profiling was performed using qPCR, and ELISA, in situ hybridization and immunohistochemistry were applied for the presentation of their cellular localization. We demonstrated that miR-21 as well as CCL20 were both significantly upregulated in CRC tissues; thus, showing no antidromic expression pattern. This provided an initial clue that miR-21 and CCL20 may not be expressed in the same cell. In addition, we located miR-21 expression at the cellular level predominantly in stromal cells such as tumor-associated fibroblasts and to a minor degree in immune cells such as macrophages and lymphocytes. Likewise, CCL20 expression was primarily detected in tumor-infiltrating immune cells. Thus, investigating the cellular localization of miR-21 and its target CCL20 revealed that both molecules are expressed predominantly in the microenvironment of CRC tumors.