Department of Magnetic Resonance, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
DNA Cell Biol. 2021 Jan;40(1):93-100. doi: 10.1089/dna.2020.5442. Epub 2020 Nov 12.
Glioblastoma multiforme (GBM) is characterized by diffuse infiltration of the brain, active regional recurrence, low cure proportion, and limited chemotherapy efficiency. is a component of the mismatch repair system related to the oncogenesis, tumor evolution, and recurrence of GBM. The impact of upregulation on the tumor microenvironment (TME) of GBM and the feasibility of as a potential target to improve the prognosis remain unknown. The expression of at mRNA level indicated that expressed higher in GBM tissues than that in normal ones. The transwell assay and expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) suggested that the capability of invasion and migration in U251-MSH6 was more stubborn. The intracranial tumor model was established with nude mice to further explore . The time-weight curve, overall survival, tumor volumes, expression levels of MMP-2 and MMP-9 in tissue, and hematoxylin and eosin staining all indicated that had a positive effect on metastasis. The expression levels of related proteins suggested that the hypoxia TME induced by may promote metastasis via epithelial to mesenchymal transition, stemness, and angiogenesis progress. is an overexpressed oncogene in human GBM tissues, which accelerated metastasis by regulating hypoxia inducible factor-1A (HIF1A) to form a hypoxic TME in GBM. The was a vital marker of GBM, making it a promising therapeutic target.
多形性胶质母细胞瘤（GBM）的特征是脑内弥漫浸润、区域性复发活跃、治愈率低、化疗效果有限。MSH6 是与 GBM 的发生、肿瘤演进和复发相关的错配修复系统的一个组成部分。MSH6 上调对 GBM 肿瘤微环境（TME）的影响，以及 MSH6 作为改善预后的潜在靶点的可行性尚不清楚。在 mRNA 水平上的表达表明，MSH6 在 GBM 组织中的表达高于正常组织。Transwell 分析和基质金属蛋白酶-2（MMP-2）和基质金属蛋白酶-9（MMP-9）的表达水平表明，U251-MSH6 的侵袭和迁移能力更顽固。通过建立裸鼠颅内肿瘤模型进一步探讨 MSH6。时间-重量曲线、总生存期、肿瘤体积、组织中 MMP-2 和 MMP-9 的表达水平以及苏木精和伊红染色均表明 MSH6 对转移有积极作用。相关蛋白的表达水平表明，MSH6 诱导的缺氧 TME 通过上皮间质转化、干性和血管生成进展促进转移。MSH6 是人类 GBM 组织中过表达的癌基因，它通过调节缺氧诱导因子-1A（HIF1A）在 GBM 中形成缺氧 TME 来加速转移。MSH6 是 GBM 的一个重要标志物，使其成为一种有前途的治疗靶点。
