Fkih M'hamed Insaf, Privat Maud, Trimeche Mounir, Penault-Llorca Frédérique, Bignon Yves-Jean, Kenani Abderraouf
Departement of oncogenetics, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France.
EA4677 ERTICA, University of Auvergne, Clermont-Ferrand, France.
Pathol Oncol Res. 2017 Oct;23(4):815-827. doi: 10.1007/s12253-017-0188-4. Epub 2017 Jan 18.
MicroRNAs (miRNAs) are small non-coding RNAs composed of 18-25 nucleotides that can post-transcriptionally regulate gene expression and have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. About 1000 genes in humans encode miRNAs, which account for approximately 3% of the human genome, and up to 30% of human protein coding genes may be regulated by miRNAs. The objective of this article is to evaluate the expression profile of four miRNAs previously implicated in triple negative breast cancer: miR-10b, miR-26a, miR-146a and miR-153, and to determine their possible interaction in triple negative and non triple negative breast cancer based on clinical outcome and the expression of BRCA1. 24 triple-negative and 13 non triple negative breast cancer cases, were studied by q-RT-PCR and immunohistochemistry to determine the expression of the four studied miRNAs and the BRCA1 protein, respectively. We observed that the BRCA1 protein was absent in 62.5% of the triple negative cases. Besides, the miR-146a and miR-26a were over expressed in triple negative breast cancer. These two miRNAs, miR-10b and miR-153 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma. All the analyzed microRNAs were not associated with the expression of BRCA1 in our conditions. Our work provides evidence that miR-146a, miR-26a, miR-10b and miR-153 could be defined as biomarkers in triple negative breast cancer to predict lymph node metastases (LNM).
微小RNA(miRNA)是由18 - 25个核苷酸组成的小型非编码RNA,可在转录后调节基因表达,在癌症中发挥关键调节作用,兼具癌基因和肿瘤抑制基因的功能。人类约有1000个基因编码miRNA,约占人类基因组的3%,且高达30%的人类蛋白质编码基因可能受miRNA调控。本文的目的是评估先前与三阴性乳腺癌相关的四种miRNA:miR - 10b、miR - 26a、miR - 146a和miR - 153的表达谱,并根据临床结果和BRCA1的表达确定它们在三阴性和非三阴性乳腺癌中的可能相互作用。通过q - RT - PCR和免疫组织化学分别研究了24例三阴性和13例非三阴性乳腺癌病例,以确定四种研究的miRNA和BRCA1蛋白的表达。我们观察到62.5%的三阴性病例中不存在BRCA1蛋白。此外,miR - 146a和miR - 26a在三阴性乳腺癌中过表达。这两种miRNA,miR - 10b和miR - 153与三阴性乳腺癌中淋巴结转移的发生显著相关。在我们的研究条件下,所有分析的微小RNA均与BRCA1的表达无关。我们的工作提供了证据,表明miR - 146a、miR - 26a、miR - 10b和miR - 153可被定义为三阴性乳腺癌中预测淋巴结转移(LNM)的生物标志物。