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循环及组织微小RNA-21与组织程序性细胞死亡蛋白4表达及伊拉克女性乳腺肿瘤侵袭性的相互关系

Interrelation of the Circulating and Tissue MicroRNA-21 with Tissue PDCD4 Expression and the Invasiveness of Iraqi Female Breast Tumors.

作者信息

Abdulhussain Meena M, Hasan Najat A, Hussain Alaa G

机构信息

1Department of Chemistry and Biochemistry, College of Medicine, Alnahrain University, Baghdad, Iraq.

2Department of Clinical Pathology, College of Medicine, Alnahrain University, Baghdad, Iraq.

出版信息

Indian J Clin Biochem. 2019 Jan;34(1):26-38. doi: 10.1007/s12291-017-0710-1. Epub 2017 Nov 14.

Abstract

The changes in the translational repression and variation in mRNA degradation induced by micro RNA are important aspects of tumorigenesis. The association of microRNA-21 with clinicopathologic features and expression of programed cell death 4 (PDCD4) in Iraqi female's with breast tumors has not been studied. MicroRNAs were extracted from a set of 60 breast tumor tissues and blood samples of females with breast cancer and benign breast lesions obtained after breast-reductive surgery, and only blood samples from 30 normal volunteers. These extracts were evaluated for miR-21 expression by quantitative RT-PCR. Analysis of PDCD4 protein expression was carried out as miR-21 target gene by immunohistochemical tests and correlating the results with patients' clinicopathological features. Significant overexpression of miRNA-21 was found in breast cancer group. The fold increase in the miR-21 gene expression was significantly higher in circulating exosomes and breast tissues of breast cancer patients as compared to other groups ( < 0.001). Overexpression of miR-21 was also significantly associated with the advanced tumor stage and histological grade. In breast cancer patients, PDCD4 protein expression was decreased to about 70% of the level in the control group. The delta Ct of exosomal and breast tissue miRNA-21 was negatively associated with PDCD4 expression. , the translational repression of the PDCD4 induced by the high expression of miR-21 promotes breast cell transformation and development of breast tumor, and circulating miR-21 level could be applied to the screening panels for early detection of women breast cancer.

摘要

微小RNA诱导的翻译抑制变化和mRNA降解差异是肿瘤发生的重要方面。尚未研究微小RNA-21与伊拉克女性乳腺肿瘤的临床病理特征及程序性细胞死亡4(PDCD4)表达之间的关联。从一组60例乳腺肿瘤组织以及乳腺癌和良性乳腺病变女性患者在乳房缩小手术后获得的血液样本中提取微小RNA,正常志愿者仅取30例的血液样本。通过定量逆转录聚合酶链反应评估这些提取物中miR-21的表达。通过免疫组织化学检测对作为miR-21靶基因的PDCD4蛋白表达进行分析,并将结果与患者的临床病理特征相关联。在乳腺癌组中发现miRNA-21显著过表达。与其他组相比,乳腺癌患者循环外泌体和乳腺组织中miR-21基因表达的增加倍数显著更高(<0.001)。miR-21的过表达也与肿瘤晚期和组织学分级显著相关。在乳腺癌患者中,PDCD4蛋白表达降至对照组水平的约70%。外泌体和乳腺组织miRNA-21的△Ct与PDCD4表达呈负相关。因此,miR-21高表达诱导的PDCD4翻译抑制促进乳腺细胞转化和乳腺肿瘤发展,循环miR-21水平可应用于女性乳腺癌早期检测的筛查指标。

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