通过构建lncRNAs调控模型对癌症管腔亚型的DRAIC和TP53TG1进行综合分析。

IF 2.9
Breast cancer (Tokyo, Japan) Pub Date : 2022-11-01 Epub Date: 2022-07-24 DOI:10.1007/s12282-022-01385-7
Jamshid Motalebzadeh, Elaheh Eskandari
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引用次数: 2

摘要

背景:破译与乳腺癌亚型相关的新分子对预后和确定更好的靶向治疗策略至关重要。在本研究中,我们旨在模拟乳腺癌管腔A和管腔B亚型中的ceRNAs网络,然后深入研究两种候选lncrna在乳腺肿瘤中的作用。方法:我们基于先前鉴定的转录因子(tf)和mirna与相关lncrna构建了两个网络作为调控模型。然后,我们利用可用的在线数据库强调了一些lncrna在乳腺癌腔内亚型中的作用。此外,我们通过经验量化了两种候选lncrna (drac和TP53TG1)在乳腺肿瘤和正常组织中的表达水平。结果:在这里,我们提出了TFs-miRNAs-lncRNAs在乳腺癌腔内亚型中的调控模型。我们分别在luminal A和luminal B亚型中发现了18和17个差异表达的lncrna。在这些lncrna中,16个与乳腺癌患者的RFS和/或OS率相关。众所周知的lncrna如HOTAIR和MALAT1被确定为与这两个网络中患者生存率相关的中心因素。基于我们综合的计算机数据分析结果,我们对两个鲜为人知的lncrna, dric和TP53TG1进行了临床实验,发现它们与乳腺癌腔内亚型之间存在显著关联。有趣的是,我们发现DRAIC和TP53TG1 lncrna与乳腺癌患者ER和pr阳性样本和淋巴结侵袭之间存在显著关联。结论:根据研究结果,DRAIC和TP53TG1 lncrna在乳腺肿瘤中过表达,可能在乳腺癌腔内亚型中起致瘤作用,对预后有中等影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comprehensive analysis of DRAIC and TP53TG1 in breast cancer luminal subtypes through the construction of lncRNAs regulatory model.

Background: Deciphering new molecules related to the breast cancer subtypes is crucial for prognosis and determining a better strategy for targeted therapy. In this study, we aimed to model ceRNAs networks in luminal A and luminal B subtypes of breast cancer and then delve deeper into the role of two candidate lncRNAs in breast tumors.

Methods: We constructed two networks as a regulatory model based on our previously identified transcription factors (TFs) and miRNAs with associated lncRNAs. Then, we highlighted the role of some lncRNAs in luminal subtypes of breast cancer using available online databases. Furthermore, we empirically quantified the expression levels of two candidate lncRNAs (DRAIC and TP53TG1) in breast tumors and normal tissues.

Results: Here, we proposed a regulatory model for TFs-miRNAs-lncRNAs in luminal subtypes of breast cancer. We found 18 and 17 differentially expressed lncRNAs in luminal A and luminal B subtypes, respectively. Of these lncRNAs, 16 were associated with breast cancer patients' RFS and/or OS rates. Well-known lncRNAs like HOTAIR and MALAT1 were identified as central factors associated with patients' survival rates in both networks. Based on the results acquired from our comprehensive in-silico data analysis, we carried out clinical experiments on two less-known lncRNAs, DRAIC and TP53TG1, and found a significant association between them with luminal subtypes of breast cancer. Interestingly, we discovered a significant association between DRAIC and TP53TG1 lncRNAs with ER- and PR-positive samples and lymph-node invasion in breast cancer patients.

Conclusion: According to the results, DRAIC and TP53TG1 lncRNAs are overexpressed in breast tumors and may play an oncogenic role with a moderate value of prognosis for luminal subtypes of breast cancer.

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