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miR-15b/HOTAIR/p53 形成一个调节环路,影响神经胶质瘤细胞的生长。

MiR-15b/HOTAIR/p53 form a regulatory loop that affects the growth of glioma cells.

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Department of Neurosurgery, The First People's Hospital of Yancheng, The Forth Affiliated Hospital of Nantong University, Yancheng, China.

出版信息

J Cell Biochem. 2018 Jun;119(6):4540-4547. doi: 10.1002/jcb.26591. Epub 2018 Feb 28.

Abstract

Among the malignant tumors of the human central nervous system, gliomas have the highest incidence and recurrence rate. Therefore, exploration of the molecular mechanism that underlies the development and progression of gliomas is of great clinical significance. Many studies have demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the development and progression of tumors. In the present study, both an RNAhybrid analysis and a dual-luciferase reporter gene assay confirmed that microRNA-15b (miR-15b) binding sites were present in the sequence of HOX transcript antisense RNA (HOTAIR). The present study further demonstrated that miR-15b, HOTAIR, and p53 formed a mutually regulated loop. MiR-15b upregulated the expression of p53 but inhibited the expression of HOTAIR. In addition, miR-15b was able to regulate the expression of HOTAIR through p53. P53 promoted miR-15b expression but inhibited HOTAIR expression. Furthermore, the examination of cell proliferation, apoptosis, and invasion revealed that both miR-15b and p53 inhibited the proliferation and invasion, but promoted the apoptosis, of glioma cells. In contrast, HOTAIR exerted effects that were the opposite of those exerted by miR-15b and p53 on glioma cells. The upregulation of HOTAIR suppressed the inhibitory effects of miR-15b and p53 on cell proliferation and invasion as well as the promoting effect of miR-15b and p53 on apoptosis. Therefore, it can be concluded that miR-15b, HOTAIR, and p53 constitute a regulatory loop that is capable of regulating the growth of glioma cells. This finding provides a new target for the treatment of gliomas.

摘要

在人类中枢神经系统的恶性肿瘤中,神经胶质瘤的发病率和复发率最高。因此,探索神经胶质瘤发生和发展的分子机制具有重要的临床意义。许多研究表明,长链非编码 RNA(lncRNA)和 microRNA(miRNA)在肿瘤的发生和发展中发挥重要作用。本研究通过 RNAhybrid 分析和双荧光素酶报告基因检测证实,miR-15b(miR-15b)的结合位点存在于 HOX 转录反义 RNA(HOTAIR)的序列中。本研究进一步证实,miR-15b、HOTAIR 和 p53 形成了相互调节的环路。miR-15b 上调 p53 的表达,但抑制 HOTAIR 的表达。此外,miR-15b 可以通过 p53 调节 HOTAIR 的表达。p53 促进 miR-15b 的表达,但抑制 HOTAIR 的表达。进一步研究细胞增殖、凋亡和侵袭发现,miR-15b 和 p53 均抑制神经胶质瘤细胞的增殖和侵袭,但促进其凋亡。相反,HOTAIR 对神经胶质瘤细胞的作用与 miR-15b 和 p53 的作用相反。HOTAIR 的上调抑制了 miR-15b 和 p53 对细胞增殖和侵袭的抑制作用以及 miR-15b 和 p53 对细胞凋亡的促进作用。因此,可以得出结论,miR-15b、HOTAIR 和 p53 构成了一个调节环路,能够调节神经胶质瘤细胞的生长。这一发现为神经胶质瘤的治疗提供了新的靶点。

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