miR-21 和 Notch-1 在人结直肠癌细胞中的过度表达与临床分期的相关性。
Correlation of over-expressions of miR-21 and Notch-1 in human colorectal cancer with clinical stages.
机构信息
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China.
Department of Pharmacology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Department of Pharmacology, School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan 610083, PR China.
出版信息
Life Sci. 2014 Jun 13;106(1-2):19-24. doi: 10.1016/j.lfs.2014.04.017. Epub 2014 Apr 26.
AIM
The aim of the study was to identify expressions of Notch-1, microRNA-21 (miR-21), and phosphatase and tensin homolog (PTEN) in colorectal cancer (CRC), and to explore their relationship with clinical stages and metastatic status of CRC.
MAIN METHODS
102 CRC patients were enrolled and clinical data were analyzed. Expressions of Notch-1 and miR-21 in CRC and adjacent non-tumor tissues of these patients were measured by real time-PCR. Protein expressions of Notch-1 and PTEN of 12 paired tissues were determined by Western blot and immunohistochemistry. The correlations between gene expressions in different clinical stages as well as metastatic status were evaluated by linear regression.
KEY FINDINGS
Notch-1 was over-expressed in 86.27% (88/102) CRC tissues, particularly in advanced stages, while miR-21 expression was increased to 74.51% (76/102) in CRC tissues compared with matched adjacent non-tumor tissues. The expressions of Notch-1 and miR-21 were positively correlated with CRC development, especially in advanced-stages (r(2)=0.3839, p<0.01). Expressions of PTEN were significantly down-regulated in CRC tissues and negatively correlated with expressions of Notch-1 (r(2)=0.5207, p<0.01) and miR-21 (r(2)=0.6996, p<0.01).
SIGNIFICANCE
These data indicate that the crosstalk between Notch-1 and miR-21 is involved in CRC development through degradation of PTEN.
目的
本研究旨在鉴定 Notch-1、microRNA-21（miR-21）和磷酸酶张力蛋白同源物（PTEN）在结直肠癌（CRC）中的表达，并探讨其与 CRC 临床分期和转移状态的关系。
主要方法
纳入 102 例 CRC 患者并分析其临床资料。采用实时 PCR 法检测这些患者 CRC 及相邻非肿瘤组织中 Notch-1 和 miR-21 的表达。采用 Western blot 和免疫组化法检测 12 对组织中 Notch-1 和 PTEN 的蛋白表达。采用线性回归评估不同临床分期和转移状态下基因表达的相关性。
主要发现
Notch-1 在 86.27%（88/102）CRC 组织中呈过表达，尤其是在晚期，而 miR-21 在 CRC 组织中的表达则较匹配的相邻非肿瘤组织升高至 74.51%（76/102）。Notch-1 和 miR-21 的表达与 CRC 的发生呈正相关，尤其是在晚期（r²=0.3839，p<0.01）。PTEN 在 CRC 组织中的表达明显下调，与 Notch-1（r²=0.5207，p<0.01）和 miR-21（r²=0.6996，p<0.01）的表达呈负相关。
意义
这些数据表明，Notch-1 和 miR-21 之间的串扰通过降解 PTEN 参与 CRC 的发生。
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