Aslan Ezgi, Akbas Emre, Yilmaz Sena, Karaoglu Ahmet Salih, Telli Ubeyde, Yildirim Salih, Gudek Hilal, Kalcioglu Mahmut Tayyar, Yilmaz Sarenur, Akalin Ibrahim
Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey.
Department of Otorhinolaryngology, Istanbul Medeniyet University Faculty of Medicine, Istanbul, Turkey.
North Clin Istanb. 2018 Sep;5(3):238-245. doi: 10.14744/nci.2017.26680.
The molecular events underlying ear development involve numerous regulatory molecules; however, the role of microRNAs (miRNAs) has not been explored in patients with ear atresia. Here, we aimed to investigate the expressions of 20-22 nucleotide noncoding RNAs.
We selected 12 miRNAs that function to control post-transcriptional gene expression in different pathways, including apoptosis, angiogenesis, and chondrogenesis. The altered miRNA expressions were analyzed by real-time PCR from serum samples of 7 patients with ear atresia and 8 controls.
We found that the expression of apoptosis-regulating miRNAs was significantly downregulated in patients with ear atresia. TThe expressions of miR126, miR146a, miR222, and miR21 were significantly decreased by 76.2-(p=0.041), 61.8-(p=0.000), 30.5-(p=0.009), and 71.21-fold (p=0.042), respectively, compared with controls.
Abnormal ear development in ear atresia patients, could possibly be due to the reduced expression of apoptosis regulating miRNAs. Changes in the regulation of tumor protein p53 (TP53), p53 upregulated modulator of apoptosis (PUMA), Fas cell surface death receptor (FAS), FAS ligand (FasL), and phosphatase and tensin homolog (PTEN) directly or within the apoptosis-related cascades may play important roles during development, particularly in the external ear. This is the first report to present the possible association between apoptosis-regulating miRNAs and ear atresia/microtia.
耳部发育的分子事件涉及众多调控分子;然而,微小RNA(miRNA)在耳部闭锁患者中的作用尚未得到探索。在此,我们旨在研究20 - 22个核苷酸非编码RNA的表达情况。
我们选择了12种在不同途径(包括细胞凋亡、血管生成和软骨生成)中发挥转录后基因表达调控作用的miRNA。通过实时聚合酶链反应对7例耳部闭锁患者和8例对照者的血清样本中miRNA表达的变化进行分析。
我们发现,耳部闭锁患者中调控细胞凋亡的miRNA表达显著下调。与对照组相比,miR126、miR146a、miR222和miR21的表达分别显著降低了76.2倍(p = 0.041)、61.8倍(p = 0.000)、30.5倍(p = 0.009)和71.21倍(p = 0.042)。
耳部闭锁患者耳部发育异常可能是由于调控细胞凋亡的miRNA表达降低所致。肿瘤蛋白p53(TP53)、p53上调凋亡调节因子(PUMA)、Fas细胞表面死亡受体(FAS)、FAS配体(FasL)以及磷酸酶和张力蛋白同源物(PTEN)在细胞凋亡相关级联反应中直接或间接的调控变化可能在发育过程中发挥重要作用,尤其是在外耳发育中。这是首篇报道调控细胞凋亡的miRNA与耳部闭锁/小耳畸形之间可能存在关联的研究。