Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Neurooncol. 2018 Jun;138(2):261-270. doi: 10.1007/s11060-018-2809-5. Epub 2018 Feb 23.
Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we investigated the expression pattern of ANCR in the course of neural differentiation. Moreover, we used published RNAseq data and clinical samples to evaluate the alteration of ANCR expression in different cell types and brain tumors. Furthermore, we manipulated ANCR expression in glioma cell lines to clarify a potential functional role for ANCR in tumorigenesis. Our qRT-PCR results revealed a significant upregulation of ANCR in more malignant and less differentiated types of brain tumors (P = 0.03). This data was in accordance with down regulation of ANCR during neural differentiation. ANCR suppression caused an elevation in apoptosis rate, as well as a G1 cell cycle arrest in glioblastoma cell line. Altogether, our data demonstrated that ANCR may play a role in glioma genesis and that it could be considered as a potential diagnostic and therapeutic target to combat brain cancers.
长非编码 RNA(lncRNA)是多种细胞和分子事件的重要调节因子,包括与癌症相关的途径。抗分化 ncRNA(ANCR)是角质形成细胞分化的关键调节剂,其表达对于维持表皮祖细胞是必需的。在此,我们研究了 ANCR 在神经分化过程中的表达模式。此外,我们使用已发表的 RNAseq 数据和临床样本评估了 ANCR 在不同细胞类型和脑肿瘤中的表达变化。此外,我们在神经胶质瘤细胞系中操纵 ANCR 的表达,以阐明 ANCR 在肿瘤发生中的潜在功能作用。我们的 qRT-PCR 结果显示,在更恶性和分化程度更低的脑肿瘤类型中,ANCR 的表达显著上调(P=0.03)。这一数据与神经分化过程中 ANCR 的下调一致。ANCR 抑制导致神经母细胞瘤细胞系中的凋亡率升高和 G1 细胞周期停滞。总之,我们的数据表明,ANCR 可能在神经胶质瘤的发生中发挥作用,它可以被认为是对抗脑癌的潜在诊断和治疗靶标。