XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-κB signalling.
XBP1-elicited environment by chemotherapy potentiates repopulation of tongue cancer cells by enhancing miR-22/lncRNA/KAT6B-dependent NF-κB signalling.
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XBP1-化疗引起的环境通过增强 miR-22/lncRNA/KAT6B-依赖性 NF-κB 信号传导来增强舌癌细胞的增殖
DOI：
10.1002/ctm2.1166
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发表时间：
2023-01
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
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作者：
细胞毒治疗后残留的肿瘤细胞引起的肿瘤再增殖已经在临床和生物学上得到了描述，但其机制尚不清楚。在这里，我们的目标是研究在死亡细胞中的肿瘤促进作用和在存活的舌癌细胞中肿瘤再生长的机制。荧光素酶活性代表肿瘤在体外和体内的再生长。使用细胞因子阵列鉴定条件培养液(CM)中差异表达的细胞因子。使用抑制剂、中和抗体、shRNAs和异位过表达策略来研究功能的获得或丧失。我们发现，正在死亡的肿瘤细胞经过细胞毒治疗后，在体外和体内都能促进活着的舌癌细胞的生长。垂死的肿瘤细胞通过细胞毒治疗诱导的内质网应激，创造基于双调节蛋白(AREG)和碱性成纤维细胞生长因子(BFGF)的细胞外环境。这种环境通过激活赖氨酸乙酰转移酶6B(KAT6B)依赖的核因子-kappaB(NF-κB)信号在活的肿瘤细胞中刺激生长。作为NF-κB的直接靶点，miR-22靶向抑制KAT6B的表达，而长非编码RNA(LncRNAs)(XLOC_003973和XLOC_010383)则拮抗MIR-22促进KAT6B表达的作用。此外，我们还检测了X-box结合蛋白-1(XBP1)激活的舌癌患者在细胞毒治疗后血液中AREG和bFGF蛋白水平的升高，发现XBP1激活与患者的预后不良有关。我们还检测到与配对的原发舌癌相比，复发性舌癌中miR-22/LncRNA/KAT6B/NF-κB信号的激活。我们确定了舌癌细胞死亡诱导肿瘤再增殖的分子机制。这些见解为确定预测性生物标记物和有效应对癌症进展提供了新的途径。
Tumour repopulation initiated by residual tumour cells in response to cytotoxic therapy has been described clinically and biologically, but the mechanisms are unclear. Here, we aimed to investigate the mechanisms for the tumour‐promoting effect in dying cells and for tumour repopulation in surviving tongue cancer cells. Tumour repopulation in vitro and in vivo was represented by luciferase activities. The differentially expressed cytokines in the conditioned medium (CM) were identified using a cytokine array. Gain or loss of function was investigated using inhibitors, neutralising antibodies, shRNAs and ectopic overexpression strategies. We found that dying tumour cells undergoing cytotoxic therapy increase the growth of living tongue cancer cells in vitro and in vivo. Dying tumour cells create amphiregulin (AREG)‐ and basic fibroblast growth factor (bFGF)‐based extracellular environments via cytotoxic treatment‐induced endoplasmic reticulum stress. This environment stimulates growth by activating lysine acetyltransferase 6B (KAT6B)‐dependent nuclear factor‐kappa B (NF‐κB) signalling in living tumour cells. As direct targets of NF‐κB, miR‐22 targets KAT6B to repress its expression, but long noncoding RNAs (lncRNAs) (XLOC_003973 and XLOC_010383) counter the effect of miR‐22 to enhance KAT6B expression. Moreover, we detected increased AREG and bFGF protein levels in the blood of tongue cancer patients with X‐box binding protein‐1 (XBP1) activation in tumours under cytotoxic therapy and found that XBP1 activation is associated with poor prognosis of patients. We also detected activation of miR‐22/lncRNA/KAT6B/NF‐κB signalling in recurrent cancers compared to paired primary tongue cancers. We identified the molecular mechanisms of cell death‐induced tumour repopulation in tongue cancer. Such insights provide new avenues to identify predictive biomarkers and effective strategies to address cancer progression.
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Diana-LNCBASE：长期非编码RNA上经过实验验证和计算预测的microRNA靶标。
影响因子：
14.9
作者：
Paraskevopoulou MD;Georgakilas G;Kostoulas N;Reczko M;Maragkakis M;Dalamagas TM;Hatzigeorgiou AG
通讯作者：
Hatzigeorgiou AG
影响因子：
64.5
作者：
Cubillos-Ruiz JR;Silberman PC;Rutkowski MR;Chopra S;Perales-Puchalt A;Song M;Zhang S;Bettigole SE;Gupta D;Holcomb K;Ellenson LH;Caputo T;Lee AH;Conejo-Garcia JR;Glimcher LH
通讯作者：
Glimcher LH
影响因子：
3.9
作者：
Wang S;Qin Y;Wang Z;Xiang J;Zhang Y;Xu M;Li B;Xia Y;Zhang P;Wang H
通讯作者：
Wang H
垂死的神经胶质瘤细胞通过 caspase 3 依赖性机制建立促血管生成微环境
影响因子：
9.7
作者：
Feng X;Yu Y;He S;Cheng J;Gong Y;Zhang Z;Yang X;Xu B;Liu X;Li CY;Tian L;Huang Q
通讯作者：
Huang Q
影响因子：
12.4
作者：
通讯作者：
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