Xing Wenli, Zeng Chun
Department of Neurosurgery, Suining Central Hospital, Suining, China.
Tumour Biol. 2017 May;39(5):1010428317705339. doi: 10.1177/1010428317705339.
Malignant glioma is one of the most common primary brain tumors that develop via multiple pathways and gene deregulation. MicroRNAs are involved in human cancer development and progression, and their serum expression profiles of glioma patients may be useful for classifying cancers. However, the profile and molecular mechanism of serum microRNAs for human glioma are poorly understood. Thus, it is crucial to analyze microRNA expression in human glioma serum to identify molecular subclasses and early stage of glioma. In this study, we performed microRNA alteration that contributes to glioma profile via analysis of The Cancer Genome Atlas RNA sequencing data and other independent Gene Expression Omnibus microarray data. We identified the glioma-associated novel microRNA as a key regulator of human glioma development and progression. The putative novel miR-1825 was validated by real-time polymerase chain reaction and its expression was significantly decreased in the serum of glioma patients compared with healthy controls. Patients with high miR-1825 expression had a longer survival rate. Interestingly, we found that miR-1825 expression levels were dependent on tumor size and pathological grading in glioma patients, but not associated with other factors including age and T classification. MicroRNA-Gene Ontology network indicated that miR-1825 may play an important role in the development of human glioma including apoptosis, cell proliferation, and invasion. In vitro assays of miR-1825 inhibit U87 cell proliferation and invasion and induce apoptosis. Furthermore, we provide evidence that the tumor-suppressive microRNA miR-1825 controls KLF2 expression. Reporter gene analyses revealed that both microRNAs directly targeted the 3'-untranslated region of KLF2 messenger RNA. These data demonstrated that miR-1825 expression in serum of human glioma was associated with tumorigenesis and miR-1825 may be used as a biomarker for identification of the pathological grade of glioma.
恶性胶质瘤是最常见的原发性脑肿瘤之一，其通过多种途径和基因失调发展而来。微小RNA参与人类癌症的发生和发展，胶质瘤患者的血清表达谱可能有助于癌症分类。然而，人类胶质瘤血清微小RNA的谱和分子机制尚不清楚。因此，分析人类胶质瘤血清中的微小RNA表达以识别胶质瘤的分子亚类和早期阶段至关重要。在本研究中，我们通过分析癌症基因组图谱RNA测序数据和其他独立的基因表达综合微阵列数据，进行了有助于胶质瘤谱的微小RNA改变分析。我们鉴定出胶质瘤相关的新型微小RNA是人类胶质瘤发生和发展的关键调节因子。通过实时聚合酶链反应验证了推定的新型miR-1825，与健康对照相比，其在胶质瘤患者血清中的表达显著降低。miR-1825表达高的患者生存率更长。有趣的是，我们发现miR-1825表达水平取决于胶质瘤患者的肿瘤大小和病理分级，但与包括年龄和T分类在内的其他因素无关。微小RNA-基因本体网络表明，miR-1825可能在人类胶质瘤的发生中发挥重要作用，包括细胞凋亡、细胞增殖和侵袭。miR-1825的体外实验抑制U87细胞增殖和侵袭并诱导细胞凋亡。此外，我们提供证据表明肿瘤抑制性微小RNA miR-1825控制KLF2表达。报告基因分析显示，两种微小RNA均直接靶向KLF2信使RNA的3'非翻译区。这些数据表明，人类胶质瘤血清中miR-1825的表达与肿瘤发生相关，miR-1825可作为识别胶质瘤病理分级的生物标志物。
