Ding Fengqin, Chen Ping, Bie Pengfei, Piao Wenhua, Cheng Quan
Department of Clinical Laboratory, People's Hospital of Ningxia Hui Autonomous Region, First Affiliated Hospital of Northwest Minzu University, Yinchuan, China.
Medical Experiment Center, General Hospital of Ningxia Medical University, Yinchuan, China.
Front Oncol. 2021 Aug 17;11:633430. doi: 10.3389/fonc.2021.633430. eCollection 2021.
Glioma is malignant tumor derives from glial cells in the central nervous system. High-grade glioma shows aggressive growth pattern, and conventional treatments, such as surgical removal and chemo-radiotherapy, archive limitation in the interference of this process. In this work, HOXA5, from the HOX family, was identified as a glioma cell proliferation-associated factor by investigating its feature in the TCGA and CGGA data set. High HOXA5 expression samples contain unfavorable clinical features of glioma, including IDH wild type, un-methylated MGMT status, non-codeletion 1p19q status, malignant molecular subtype. Survival analysis indicates that high HOXA5 expression samples are associated with worse clinical outcome. The CNVs and SNPs profile difference further confirmed the enrichment of glioma aggressive related biomarkers. In the meantime, the activation of DNA damage repair-related pathways and TP53-related pathways is also related to HOXA5 expression. In cell lines, U87MG and U251, by interfering HOXA5 expression significantly inhibit glioma progression and apoptosis, and cell cycle is arrested at the G2/M phase. Collectively, increased HOXA5 expression can promote glioma progression affecting glioma cell proliferation.
胶质瘤是源自中枢神经系统胶质细胞的恶性肿瘤。高级别胶质瘤表现出侵袭性生长模式,而传统治疗方法,如手术切除和放化疗,在干预这一过程方面存在局限性。在这项研究中,通过在TCGA和CGGA数据集中研究HOXA5的特征,发现来自HOX家族的HOXA5是一种与胶质瘤细胞增殖相关的因子。HOXA5高表达样本具有胶质瘤的不良临床特征,包括异柠檬酸脱氢酶(IDH)野生型、O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)未甲基化状态、1p19q非共缺失状态、恶性分子亚型。生存分析表明,HOXA5高表达样本与更差的临床结局相关。拷贝数变异(CNVs)和单核苷酸多态性(SNPs)图谱差异进一步证实了胶质瘤侵袭相关生物标志物的富集。同时,DNA损伤修复相关通路和TP53相关通路的激活也与HOXA5表达有关。在细胞系U87MG和U251中,通过干扰HOXA5表达可显著抑制胶质瘤进展和细胞凋亡,细胞周期停滞在G2/M期。总体而言,HOXA5表达增加可促进胶质瘤进展,影响胶质瘤细胞增殖。