CTGF表达具有指示性
CTGF expression is indicative
原文发布日期:2019-05-10
英文摘要:
摘要翻译:
原文链接:
Medulloblastoma (MB) is the most frequent malignant brain tumor in children and it is sub grouped into 4 entities (SHH, WNT, Group 3, and Group 4). Molecular pathways involved in these different subgroups still are evolving and can be of clinical relevance to therapy. The YAP1-CTGF axis is known to regulate cell proliferation, differentiation, and cell death; however, its role in MB is poorly explored. We aimed to investigate the role of YAP1 gene in the MB SHH cell line DAOY and evaluate cell proliferation, doubling time and 3D spheroids invasion and its consequence on CTGF regulation. We assessed CTGF expression from 22 children with MB. Lastly, we validated our findings through in silico analysis in large cohorts dataset of patients. We observed an increased
invasion rate of DAOY cells and CTGF downregulation under YAP1 knockdown (p < 0.0001). Additionally CTGF is overexpressed in MB with extensive nodularity subtype and an indicative of higher survival rates in pediatric MB (p < 0.05). Interestingly, no difference of CTGF expression was observed between molecular subgroups. These results provide new evidence of CTGF as a potential prognostic marker for MB, corroborating to the role of YAP1 in restricting MB cell.
髓母细胞瘤(MB)是儿童最常见的恶性脑肿瘤,可分为四个分子亚型(SHH型、WNT型、第3组和第4组)。这些不同亚型涉及的分子通路研究仍在不断深入,且具有临床治疗意义。YAP1-CTGF轴已知可调控细胞增殖、分化与死亡,但其在髓母细胞瘤中的作用尚不明确。本研究旨在探讨YAP1基因在MB SHH亚型DAOY细胞系中的作用,评估其对细胞增殖、倍增时间、3D肿瘤球侵袭能力的影响,及其对CTGF表达的调控机制。我们同时检测了22例髓母细胞瘤患儿的CTGF表达水平,并通过大规模患者队列的生物信息学分析验证实验结果。研究发现:敲低YAP1基因可显著增强DAOY细胞的侵袭能力并下调CTGF表达(p < 0.0001);CTGF在广泛结节型髓母细胞瘤中过表达,且与儿童患者较高生存率相关(p < 0.05);值得注意的是,各分子亚型间CTGF表达未见显著差异。本研究为CTGF作为髓母细胞瘤潜在预后标志物提供了新证据,并证实YAP1具有抑制髓母细胞瘤细胞的作用。
……