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微小RNA-155通过增强Wnt/β-连环蛋白信号通路促进胶质瘤进展。

miR-155 contributes to the progression of glioma by enhancing Wnt/β-catenin pathway.

作者信息

Yan Zhiyong, Che Shusheng, Wang Jianpeng, Jiao Yingbing, Wang Chao, Meng Qinghai

机构信息

Department of Neurosurgery, the Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, Shandong, China.

出版信息

Tumour Biol. 2015 Jul;36(7):5323-31. doi: 10.1007/s13277-015-3193-9. Epub 2015 Feb 12.

Abstract

As the most common brain tumor, glioma is featured with poor prognosis due to its resistance to current therapeutic strategies. The elucidation of etiology is believed to facilitate the development of novel effective anti-glioma treatment modalities. As a confirmed oncogenic microRNA (miRNA) in many other types of cancers, the role of miR-155 in glioma is still unknown. This study is aimed to study the role of miR-155 in the progression of glioma. Our results revealed that miR-155 was overexpressed in the collected glioma specimen, compared with noncancerous brain tissues. The suppression of miR-155 attenuated the proliferation of glioma cells and the activation of Wnt pathway. Silencing miR-155 was also able to suppress the growth of U-87 MG glioma xenografts in mice. Pearson analysis indicated that miR-155 level was inversely correlated with the abundance of HMG-box transcription factor 1 (HBP1), a strong Wnt pathway inhibitor, in glioma samples. Further experiments confirmed that miR-155 suppressed the expression of HBP1 by targeting the putative miRNA recognition elements (MREs) within its messenger RNA (mRNA) 3' untranslated region (UTR). Furthermore, HBP1 small interfering RNA (siRNA) abolished the effect of miR-155 suppression on the proliferation of glioma and the activation of Wnt pathway. Taken together, miR-155 promoted the progression of glioma by enhancing the activation of Wnt pathway. Thus, targeting miR-155 may be an effective strategy for glioma treatment.

摘要

作为最常见的脑肿瘤,胶质瘤因其对当前治疗策略的抗性而预后不良。病因的阐明被认为有助于开发新的有效抗胶质瘤治疗方法。作为许多其他类型癌症中已确认的致癌微小RNA(miRNA),miR-155在胶质瘤中的作用仍不清楚。本研究旨在探讨miR-155在胶质瘤进展中的作用。我们的结果显示,与非癌脑组织相比,收集的胶质瘤标本中miR-155过表达。miR-155的抑制减弱了胶质瘤细胞的增殖和Wnt通路的激活。沉默miR-155也能够抑制小鼠U-87 MG胶质瘤异种移植物的生长。Pearson分析表明,在胶质瘤样本中,miR-155水平与一种强大的Wnt通路抑制剂HMG盒转录因子1(HBP1)的丰度呈负相关。进一步的实验证实,miR-155通过靶向其信使RNA(mRNA)3'非翻译区(UTR)内的假定微小RNA识别元件(MRE)来抑制HBP1的表达。此外,HBP1小干扰RNA(siRNA)消除了miR-155抑制对胶质瘤增殖和Wnt通路激活的影响。综上所述,miR-155通过增强Wnt通路的激活促进胶质瘤的进展。因此,靶向miR-155可能是一种有效的胶质瘤治疗策略。

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