PDRG1 promotes the proliferation and migration of GBM cells by the MEK/ERK/CD44 pathway.
PDRG1 promotes the proliferation and migration of GBM cells by the MEK/ERK/CD44 pathway.
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DOI：
10.1111/cas.15214
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发表时间：
2022-03
期刊：
影响因子：
5.7
通讯作者：
Ren J
中科院分区：
文献类型：
--
作者：
Sun J;Xu Y;Liu J;Cui H;Cao H;Ren J
P53和DNA损伤调节基因1(PDRG1)在多种肿瘤中高表达。在这里，我们发现PDRG1在多形性胶质母细胞瘤(GBM)中过表达。然而，PDRG1在GBM中的临床意义、生物学作用和潜在的分子机制仍不清楚。PDRG1在胶质瘤中异常过表达，尤其在GBM中表达最高，且与胶质瘤不良的临床病理特征有关。风险评分、手术特征曲线分析、Kaplan-Meier曲线分析、单因素和多因素Cox回归分析表明，PDRG1是一个独立的预后指标，与胶质瘤的病情进展显著相关。构建预后诺模图来预测个体患者的生存风险。对PDRG1在肿瘤基因组图谱队列中的功能和途径进行了分析。PDRG1基因敲除可显著抑制GBM细胞在体内外的迁移和增殖。对PDRG1基因敲除的U-118 MG(U118)细胞的转录组序列分析表明，肿瘤细胞的生物调控黏附、生长和死亡、细胞运动、细胞黏附分子和蛋白多糖显著丰富。重要的是，我们发现在GBM中黏附分子分化簇44(CD44)的表达受PDRG1的调节。我们发现PDRG1通过丝裂原活化蛋白激酶(MEK)/细胞外调节蛋白激酶(ERK)/CD44途径促进GBM细胞的迁移和增殖。我们的发现提供了证据，即PDRG1上调可以预测人脑胶质瘤的进展和不良预后，特别是在异柠檬酸脱氢酶(IDH)患者中。本研究为PDRG1调控CD44在GBM细胞中的表达提供了新的证据，并可能通过MEK/ERK/CD44通路促进GBM细胞的迁移和增殖。PDRG1可能成为GBM的一种新的诊断指标和治疗靶点。我们的研究提供了证据，P53和DNA损伤调节基因1(PDRG1)的异常表达可能是胶质瘤的负面预后因素。我们研究了PDRG1在GBM细胞增殖和迁移中的作用，并阐明了PDRG1通过MEK/细胞外调节蛋白激酶/分化簇44途径发挥作用的潜在分子机制。我们的数据提供了PDRG1可能作为一个有价值的预后标志物的证据。抑制PDRG1可能是发展脑胶质瘤靶向治疗的一种可行策略。
P53 and DNA damage‐regulated gene1 (PDRG1) is overexpressed in diverse carcinomas. Here, we discover that PDRG1 is overexpressed in glioblastoma multiforme (GBM). However, the clinical significance, biological role, and underlying molecular mechanisms of PDRG1 in GBM remain unclear. PDRG1 was aberrantly overexpressed in glioma, especially prevalent in GBM, and correlated with poor clinicopathologic features of glioma. The risk score, operational feature curve analysis, Kaplan‐Meier curve, and univariate and multivariate Cox regression analysis indicated that PDRG1 was an independent prognostic indicator and significantly correlates with disease progression of glioma. A prognostic nomogram was constructed to predict the survival risk of individual patients. The function and pathway enrichment analysis of PDRG1 in The Cancer Genome Atlas cohort was performed. PDRG1 knockdown significantly inhibited the migration and proliferation of GBM cells in vitro and in vivo. Transcriptome sequencing analysis of PDRG1 knockdown U‐118 MG(U118) cells indicated that biological regulation adhesion, growth and death, cell motility, cell adhesion molecular and proteoglycans in cancer were significantly enriched. Importantly, we found that the expression of adhesion molecule cluster of differentiation 44 (CD44) was regulated by PDRG1 in GBM. We found that PDRG1 promoted the migration and proliferation of GBM cells via the mitogen‐activated protein kinase kinase (MEK)/extracellular regulated protein kinase (ERK)/CD44 pathway. Our findings provide proof that PDRG1 upregulation predicts progression and poor prognosis in human gliomas, especially in isocitrate dehydrogenase (IDH) wt glioma patients. The study provides new evidence that PDRG1 regulates the expression of CD44 in GBM cells and might promote the migration and proliferation via the MEK/ERK/CD44pathway. PDRG1 might be a novel diagnostic indicator and promising therapeutic target for GBM. Our study provides the evidence that aberrantly expressed P53 and DNA damage‐regulated gene1 (PDRG1) might be a negative prognosticator in glioma. We characterized the roles of PDRG1 in proliferation and migration of GBM cells, and delineated the underlying molecular mechanism that PDRG1 functions via the MEK/extracellular regulated protein kinase/cluster of differentiation 44 pathway. Our data provide evidence that PDRG1 might serve as a valuable prognostic marker. Inhibition of PDRG1 may be a plausible strategy for the development of the target therapy of glioma.
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影响因子：
3.9
作者：
Chen, Daliang;Li, Dengfeng;Zheng, Dahai
通讯作者：
Zheng, Dahai
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
6.4
作者：
Takami, Hirokazu;Yoshida, Akihiko;Ichimura, Koichi
通讯作者：
Ichimura, Koichi
DOI：
10.1186/s13046-016-0480-2
发表时间：
2017-01-05
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Xu T;Xiao D
通讯作者：
Xiao D
影响因子：
11.2
作者：
Xu Y;Stamenkovic I;Yu Q
通讯作者：
Yu Q