Kia Vahid, Sharif Beigli Maryam, Hosseini Vahedeh, Koochaki Ameneh, Paryan Mahdi, Mohammadi-Yeganeh Samira
Department of Medical Biotechnology and nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Islamic Azad University, East Tehran branch Campus, Tehran, Iran.
In Vitro Cell Dev Biol Anim. 2018 Oct;54(9):621-628. doi: 10.1007/s11626-018-0282-2. Epub 2018 Aug 21.
Breast cancer is the first common cancer among women worldwide. One of the major signaling pathways playing a role in the onset and progression of this disease is PI3K/Akt/mTOR, which can be inhibited by PTEN. miRNAs are small non-coding molecules that regulate the expression of their targets by inhibition or suppression, and thus, their dysregulated expression results in the development of cancer. Using various software applications predicting miRNAs and evaluating GEO microarray data, miR-144 was selected as an inhibitor of PTEN. The expression of miR-144 and PTEN was evaluated in 18 triple negative breast cancer (TNBC) clinical samples and cell lines including 4T1, MDA-MB-231, MDA-MB-468, SK-BR-3, and MCF-7 in comparison with normal cells. PTEN and miR-144 expression analysis revealed their elevated expression in MCF-7 cells. MDA-MB-468, SK-BR-3, and MDA-MB-231 cells showed decreased levels of PTEN and increased levels of miR-144. In contrast, 4T1 cells had an increased expression of PTEN and decreased expression of miR-144. In clinical samples, miR-144 was up-regulated in 22% of the cases and PTEN was down-regulated in 78% of the cases. The results showed that the expression of PTEN and miR-144 was inversely correlated in metastatic breast cancer cell lines. However, in TNBC clinical samples, there was no correlation between the expression of miR-144 and PTEN. Literature shows that there are other influencing factors affecting the expression of miRNAs. Therefore, care should be taken in interpreting the results of gene expression studies and its relation with cancer diagnosis/prognosis.
乳腺癌是全球女性中最常见的癌症。PI3K/Akt/mTOR是在该疾病的发生和发展中起作用的主要信号通路之一，它可被PTEN抑制。微小RNA（miRNA）是小的非编码分子，通过抑制或阻遏来调节其靶标的表达，因此，其表达失调会导致癌症的发生。通过使用各种预测miRNA并评估基因表达综合数据库（GEO）微阵列数据的软件应用程序，miR-144被选为PTEN的抑制剂。与正常细胞相比，在18个三阴性乳腺癌（TNBC）临床样本和细胞系（包括4T1、MDA-MB-231、MDA-MB-468、SK-BR-3和MCF-7）中评估了miR-144和PTEN的表达。PTEN和miR-144表达分析显示它们在MCF-7细胞中表达升高。MDA-MB-468、SK-BR-3和MDA-MB-231细胞显示PTEN水平降低，miR-144水平升高。相反，4T1细胞中PTEN表达增加，miR-144表达降低。在临床样本中，22%的病例中miR-144上调，78%的病例中PTEN下调。结果表明，在转移性乳腺癌细胞系中PTEN和miR-144的表达呈负相关。然而，在TNBC临床样本中，miR-144和PTEN的表达之间没有相关性。文献表明，还有其他影响因素会影响miRNA的表达。因此，在解释基因表达研究结果及其与癌症诊断/预后的关系时应谨慎。
