CircRNA VIM silence synergizes with sevoflurane to inhibit immune escape and multiple oncogenic activities of esophageal cancer by simultaneously regulating miR-124/PD-L1 axis,Cell Biology and Toxicology

当前位置： X-MOL 学术 › Cell Biol. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

CircRNA VIM silence synergizes with sevoflurane to inhibit immune escape and multiple oncogenic activities of esophageal cancer by simultaneously regulating miR-124/PD-L1 axis
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-05-20 , DOI: 10.1007/s10565-021-09613-0
Cao Gao ₁ , Yan-Jie Xu ₂ , Lei Qi ₃ , Ya-Fei Bao ₄ , Lei Zhang ₄ , Liang Zheng ₄

Affiliation

Background

Circular RNA of vimentin (circ-VIM) is a predictor for poor prognosis of acute myeloid leukemia, but we had little information on its function in esophageal cancer (EC). Here we examined the effects of circ-VIM together with sevoflurane on immune escape and multiple oncogenic activities of EC.

Methods

Bioinformatic tools, luciferase assay, and RNA immunoprecipitation were used to examine regulations between circ-VIM, miR-124-3p (miR-124), and PD-L1. CCK-8, wound healing, and Transwell assays were used to measure cell proliferation, migration, and invasion, respectively. The impacts of EC cells on cytotoxicity, proliferation, and apoptosis of CD8⁺ T cells were examined using LDH assay, CFSE staining, and Annexin V/PI staining, respectively. The in vivo tumorigenesis and lung metastases were assessed using xenograft model and tail vein injection of EC cells.

Results

Significant upregulation of circ-VIM and PD-L1 and downregulation of miR-124 were detected in EC tissues or cells. Circ-VIM sponged miR-124 and released its suppression on the downstream target PD-L1. Sevoflurane, independent of circ-VIM, also upregulated miR-124 to lower PD-L1 expression. By modulating miR-124/PD-L1 axis, silencing circ-VIM and applying sevoflurane both inhibited immune escape and multiple oncogenic activities of EC in vitro, and suppressed xenograft growth and lung metastases in vivo. The inactivation of Ras/ERK signaling pathway was involved in suppression of malignant phenotypes by silencing circ-VIM and sevoflurane treatment.

Conclusions

Silencing circ-VIM and applying sevoflurane, by separately regulating miR-124/PD-L1 axis, presented synergistic effects in inhibiting immune escape and multiple malignant phenotypes of EC cells.

Graphical abstract

中文翻译：

CircRNA VIM沉默与七氟醚协同通过同时调控miR-124/PD-L1轴抑制食管癌的免疫逃逸和多种致癌活性

背景

波形蛋白的环状 RNA (circ-VIM) 是急性髓性白血病预后不良的预测因子，但我们对其在食管癌 (EC) 中的功能知之甚少。在这里，我们检查了 circ-VIM 和七氟醚对 EC 的免疫逃逸和多种致癌活性的影响。

方法

生物信息学工具、荧光素酶测定和 RNA 免疫沉淀用于检查 circ-VIM、miR-124-3p (miR-124) 和 PD-L1 之间的调节。CCK-8、伤口愈合和 Transwell 测定分别用于测量细胞增殖、迁移和侵袭。分别使用LDH测定、CFSE染色和Annexin V/PI染色检测EC细胞对CD8 ^{+ T细胞的细胞毒性、增殖和凋亡的影响。}使用异种移植模型和尾静脉注射 EC 细胞评估体内肿瘤发生和肺转移。

结果

在 EC 组织或细胞中检测到 circ-VIM 和 PD-L1 的显着上调和 miR-124 的下调。Circ-VIM 吸收 miR-124 并释放其对下游靶标 PD-L1 的抑制。独立于 circ-VIM 的七氟醚也上调 miR-124 以降低 PD-L1 表达。通过调节 miR-124/PD-L1 轴，沉默 circ-VIM 和应用七氟醚在体外抑制 EC 的免疫逃逸和多种致癌活性，并在体内抑制异种移植物的生长和肺转移。Ras/ERK 信号通路的失活与通过沉默 circ-VIM 和七氟醚处理抑制恶性表型有关。