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基于竞争性内源 RNA 网络鉴定与急性淋巴细胞白血病进展相关的长链非编码 RNA。

Identification of lncRNAs associated with the progression of acute lymphoblastic leukemia using a competing endogenous RNAs network.

机构信息

Department of Molecular Medicine, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Research Institute for Oncology, Hematology and Cell Therapy, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Oncol Res. 2023 Feb 9;30(6):259-268. doi: 10.32604/or.2022.027904. eCollection 2022.

Abstract

Acute lymphoblastic leukemia (ALL) is a malignancy of bone marrow lymphoid precursors. Despite effective treatments, the causes of its progression or recurrence are still unknown. Finding prognostic biomarkers is needed for early diagnosis and more effective treatment. This study was performed to identify long non-coding RNAs (lncRNAs) involved in ALL progression by constructing a competitive endogenous RNA (ceRNA) network. These lncRNAs may serve as potential new biomarkers in the development of ALL. The GSE67684 dataset identified changes in lncRNAs and mRNAs involved in ALL progression. Data from this study were re-analyzed, and probes related to lncRNAs were retrieved. Targetscan, miRTarBase, and miRcode databases were used to identify microRNAs (miRNAs) related to the discovered genes and lncRNAs. The ceRNA network was constructed, and the candidate lncRNAs were selected. Finally, the results were validated with reverse transcription quantitative real-time PCR (RT-qPCR). The ceRNA network outcomes demonstrated that the top lncRNAs associated with altered mRNAs in ALL are IRF1-AS1, MCM3AP-AS1, TRAF3IP2-AS1, HOTAIRM1, CRNDE, and TUG1. Investigations of the subnets linked to MCM3AP-AS1, TRAF3IP2-AS1, and IRF1-AS1 indicated that these lncRNAs were considerably related to pathways associated with inflammation, metastasis, and proliferation. Higher expression levels of IRF1-AS1, MCM3AP-AS1, TRAF3IP2-AS1, CRNDE, and TUG1 were found in ALL samples compared to controls. The expression of MCM3AP-AS1, TRAF3IP2-AS1, and IRF1-AS1 is significantly elevated during the progression of ALL, playing an oncogenic role. Due to their role in the main cancer pathways, lncRNAs could be suitable therapeutic and diagnostic targets in ALL.

摘要

急性淋巴细胞白血病(ALL)是骨髓淋巴样前体的恶性肿瘤。尽管有有效的治疗方法,但它进展或复发的原因仍不清楚。寻找预后生物标志物对于早期诊断和更有效的治疗是必要的。本研究通过构建竞争性内源性 RNA(ceRNA)网络,旨在确定参与 ALL 进展的长非编码 RNA(lncRNA)。这些 lncRNA 可能成为 ALL 发展的潜在新生物标志物。GSE67684 数据集确定了与 ALL 进展相关的 lncRNA 和 mRNA 的变化。对本研究的数据进行了重新分析,并检索了与 lncRNA 相关的探针。使用 Targetscan、miRTarBase 和 miRcode 数据库来识别与发现的基因和 lncRNA 相关的 microRNA(miRNA)。构建了 ceRNA 网络,并选择了候选 lncRNA。最后,通过逆转录定量实时 PCR(RT-qPCR)验证了结果。ceRNA 网络的结果表明,与 ALL 中改变的 mRNA 相关的顶级 lncRNA 是 IRF1-AS1、MCM3AP-AS1、TRAF3IP2-AS1、HOTAIRM1、CRNDE 和 TUG1。对与 MCM3AP-AS1、TRAF3IP2-AS1 和 IRF1-AS1 相关的子网的研究表明,这些 lncRNA 与与炎症、转移和增殖相关的途径密切相关。与对照相比,在 ALL 样本中发现 IRF1-AS1、MCM3AP-AS1、TRAF3IP2-AS1、CRNDE 和 TUG1 的表达水平较高。在 ALL 的进展过程中,MCM3AP-AS1、TRAF3IP2-AS1 和 IRF1-AS1 的表达显著上调,发挥致癌作用。由于它们在主要癌症途径中的作用,lncRNA 可能是 ALL 中合适的治疗和诊断靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/389d/10208050/825d68663155/OncolRes-30-27904-f001.jpg

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