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lncRNA-miR-mRNA 网络对低剂量阿司匹林治疗乳腺癌患者的创新靶点。

Innovative targets of the lncRNA-miR-mRNA network in response to low-dose aspirin in breast cancer patients.

机构信息

Breast Diseases Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran.

Department of Surgery, Arash Women's Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Sci Rep. 2022 Jul 14;12(1):12054. doi: 10.1038/s41598-022-16398-7.

DOI:10.1038/s41598-022-16398-7
PMID:35835840
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9283473/
Abstract

This study aimed to investigate innovative targets in breast cancer patients by considering the interaction of the lncRNA-miR-mRNA network in response to low-dose aspirin. The candidate miRs were first taken from the GEO and TCGA databases. Then, the candidate network was constructed using the high-throughput sequencing data. The expression levels of candidate targets were finally measured using Real-Time PCR in luminal A breast cancer patients undergoing aspirin (80 mg daily for three months) and non-aspirin groups during chemotherapy after surgery. The expression levels of TGFβ, IL-17, IFNγ, and IL-β proteins were measured using the ELISA technique. 5 lncRNAs, 12 miRs, and 10 genes were obtained in the bioinformatic phase. A significant expression increase of the candidate tumor suppressor lncRNAs, miRs, and genes and a substantial expression decrease of the candidate onco-lncRNAs, oncomiRs, and oncogenes were achieved after the aspirin consumption. Unlike the non-aspirin group, the expression levels of TGFβ, IL-17, IFNγ, and IL-β proteins were significantly decreased following aspirin consumption. The Kaplan-Meier analysis indicated a longer overall survival rate in the patients after aspirin consumption. Our results showed that the lncRNA-miR-mRNA network might be a significant target for aspirin; their expression changes may be a new strategy with potential efficacy for cancer therapy or prevention.

摘要

本研究旨在通过考虑低剂量阿司匹林反应中的 lncRNA-miR-mRNA 网络相互作用，来探究乳腺癌患者的创新靶点。首先从 GEO 和 TCGA 数据库中获取候选 mirs，然后使用高通量测序数据构建候选网络，最后在接受阿司匹林（每天 80mg，持续三个月）和非阿司匹林组的手术后化疗期间，使用实时 PCR 测量腔 A 型乳腺癌患者候选靶标的表达水平。使用 ELISA 技术测量 TGFβ、IL-17、IFNγ 和 IL-β 蛋白的表达水平。在生物信息学阶段获得了 5 个 lncRNAs、12 个 mirs 和 10 个基因。在阿司匹林使用后，候选肿瘤抑制性 lncRNAs、miRs 和基因的表达显著增加，而候选癌基因 lncRNAs、oncomiRs 和癌基因的表达显著降低。与非阿司匹林组相比，阿司匹林使用后 TGFβ、IL-17、IFNγ 和 IL-β 蛋白的表达水平显著降低。Kaplan-Meier 分析表明，阿司匹林使用后患者的总生存率更高。我们的结果表明，lncRNA-miR-mRNA 网络可能是阿司匹林的一个重要靶点；它们的表达变化可能是癌症治疗或预防的一种潜在有效策略。

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