■本研究的目的是分析STAT5B通过促进p53/xCT通路的DCAF13转录调控来抑制套细胞淋巴瘤(MCL)中铁凋亡的机制。
■STAT5B,使用基因表达谱交互式分析(GEPIA,http://gepia。癌症-PKU。cn/index。html).STAT5B的表达水平和成对相关性,检测MCL患者的DCAF13、p53和xCT,分别。将STAT5B沉默以证实它们在MCL铁凋亡中的临界性。阻断坏死的作用,研究了凋亡和铁凋亡对STAT5B抗MCL作用的影响。构建具有STAT5B过表达和/或DCAF13沉默的细胞以证实DCAF13参与STAT5B调节的p53/xCT途径。DCAF13过表达和MG132证实了p53泛素化的调控。通过荷瘤裸鼠模型阐明了沉默DCAF13和MG132对MCL上STAT5B过表达的影响。
■DCAF13在MCL中过表达,与STAT5B呈正相关,与p53呈负相关,与xCT呈正相关。抑制铁凋亡减轻了siSTAT5B对MCL的抑制作用,而抑制坏死和凋亡作用不大。DCAF13的沉默导致p53/xCT和铁凋亡的STAT5B调节的阻断。DCAF13的变化和MG132的添加对p53mRNA没有统计学意义。DCAF13的升高导致p53蛋白水平的下调,MG132逆转了这种抑制作用。在动物模型中,STAT5B促进MCL和抑制铁凋亡。沉默DCAF13阻断STAT5B抑制p53和诱导xCT,GPX4和GSH。
■STAT5B通过促进DCAF13转录来调节p53/xCT通路以促进MCL进展,从而抑制铁凋亡。
UNASSIGNED: The purpose of this study was to analyze the mechanism by which STAT5B inhibits ferroptosis in mantle cell lymphoma (MCL) by promoting DCAF13 transcriptional regulation of p53/xCT pathway.
UNASSIGNED: The correlations between STAT5B, DCAF13 and ferroptosis in MCL were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA, http://gepia.cancer-pku.cn/index.html). The expression levels and pairwise correlations of STAT5B, DCAF13, p53 and xCT in MCL patients were detected, respectively. STAT5B was silenced to confirm their criticality in MCL ferroptosis. the effects of blocking necrosis, apoptosis and ferroptosis on the anti-MCL effects of STAT5B were examined. Cells with STAT5B overexpression and/or DCAF13 silencing were constructed to confirm the involvement of DCAF13 in the STAT5B-regulated p53/xCT pathway. The regulation of p53 ubiquitination was confirmed by DCAF13 overexpression and MG132. The effects of silencing DCAF13 and MG132 on STAT5B overexpression on MCL was clarified by a tumor-bearing nude mouse model.
UNASSIGNED: DCAF13 was overexpressed in MCL and positively correlated with STAT5B, negatively correlated with p53, and positively correlated with xCT. Inhibition of ferroptosis alleviated the inhibitory effects of siSTAT5B on MCL, while inhibition of necrosis and apoptosis had few effects. Silencing of DCAF13 led to the blocking of STAT5B regulation of p53/xCT and ferroptosis. The changes in DCAF13 and the addition of MG132 did not have statistically significant effects on p53 mRNA. Elevation of DCAF13 resulted in downregulation of p53 protein levels, and this inhibition was reversed by MG132. In animal models, the promotion of MCL and the inhibition of ferroptosis by STAT5B. Silencing of DCAF13 blocked STAT5B inhibition of p53 and induction of xCT, GPX4, and GSH.
UNASSIGNED: STAT5B suppresses ferroptosis by promoting DCAF13 transcription to regulate p53/xCT pathway to promote MCL progression.