Differentially expressed circular RNA profiles and comprehensive analysis of circRNA-miRNA-mRNA regulatory network in microsatellite instability-high endometrial cancer

IF 4.3 3区材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-09-01 DOI:10.1016/j.ygeno.2024.110931

Weijia Wen , Li Yuan , Xueyuan Zhao , Yan Jia , Linna Chen , Hongye Jiang , Wei Wang , Chunyu Zhang , Shuzhong Yao

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Abstract

The clinical benefit of anti-programmed cell death protein 1 (PD-1)-based immunotherapy among patients with microsatellite instable (MSI) endometrial cancer (EC) precedes that of microsatellite stable (MSS) EC, the mechanisms of which have not been fully understood. Circular RNAs (circRNAs) were reported to modulate immune evasion in several types of malignancies, while their roles in the immune regulation in EC remain largely unknown. Here, we conducted circRNA array analysis and mRNA-Sequencing of 10 MSI EC samples and 10 MSS EC samples and identified 1083 differentially expressed circRNAs (DE-circRNAs) and 864 differentially expressed mRNAs, based on which we constructed a circRNA-miRNA-mRNA comprehensive network consisting of 35 DE-circRNAs, 56 predicted miRNAs and 24 differentially expressed mRNAs. Finally, we confirmed hsa_circ_0058230 being positively correlated with CD8+ T cells infiltration, suggesting that it might take a part in anti-tumor immunity in EC.

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微卫星不稳定性高的子宫内膜癌中差异表达的环状 RNA 图谱及环状 RNA-miRNA-mRNA 调控网络的综合分析

在微卫星不稳定（MSI）子宫内膜癌（EC）患者中，基于抗程序性细胞死亡蛋白1（PD-1）的免疫疗法的临床获益先于微卫星稳定（MSS）EC，其机制尚未完全明了。据报道，环状核糖核酸（circRNAs）可调节多种恶性肿瘤的免疫逃避，但它们在子宫内膜癌免疫调节中的作用在很大程度上仍不为人所知。在此，我们对10个MSI EC样本和10个MSS EC样本进行了circRNA阵列分析和mRNA测序，发现了1083个差异表达的circRNAs（DE-circRNAs）和864个差异表达的mRNAs，并在此基础上构建了一个由35个DE-circRNAs、56个预测的miRNAs和24个差异表达的mRNAs组成的circRNA-miRNA-mRNA综合网络。最后，我们证实了 hsa_circ_0058230 与 CD8+ T 细胞浸润呈正相关，这表明它可能参与了 EC 的抗肿瘤免疫。

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