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长链非编码 RNA H19 水平升高与小儿急性淋巴细胞白血病中 miR-326 和 BCL-2 基因下调相关,这可能是白血病发生的一个标志。

Increased level of long non coding RNA H19 is correlated with the downregulation of miR-326 and BCL-2 genes in pediatric acute lymphoblastic leukemia, a possible hallmark for leukemogenesis.

机构信息

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Postal Code 81746-73441, Hazer Jarib Street, Isfahan, Iran.

出版信息

Mol Biol Rep. 2021 Feb;48(2):1531-1538. doi: 10.1007/s11033-021-06161-y. Epub 2021 Feb 12.

Abstract

Long non-coding RNAs (lncRNAs) and their role in competitive endogenous RNA (ceRNA) networks have emerged as fundamental debates in the biological processes of initiation and progression of cancer. This study aimed to identify and measure the expression levels of relevant ceRNA regulatory genes contributing to acute lymphoblastic leukemia (ALL). lncRNA H19 and BCL-2 mRNA were chosen based on in silico studies and their interactions with miR-326. Subsequently, the aforementioned coding/non-coding gene expression profiles were measured using qRT-PCR in 50 bone marrow samples, including 33 cases with pediatric ALL and 17 controls with no evidence of malignancy. lncRNA H19 was identified as an oncogenic factor which was noticeably increased in the newly diagnosed patients (P = 0.0019, AUC = 0.84) and negatively associated with miR-326 (r = -0.6, P = 0.02). Furthermore, a negative correlation was introduced between the transcriptional levels of miR-326 and the anti-apoptotic BCL-2 gene (r = -0.6, P = 0.028). The novel experimental and bioinformatic results achieved in this study may provide new insights into the molecular leukemogenesis of pediatric ALL.

摘要

长链非编码 RNA(lncRNAs)及其在竞争性内源 RNA(ceRNA)网络中的作用,已成为癌症起始和进展等生物学过程中的重要研究课题。本研究旨在鉴定和测量与急性淋巴细胞白血病(ALL)相关的 ceRNA 调控基因的表达水平。基于计算机研究,选择 lncRNA H19 和 BCL-2 mRNA 及其与 miR-326 的相互作用。随后,使用 qRT-PCR 测量了 50 个骨髓样本中的上述编码/非编码基因表达谱,其中包括 33 例儿科 ALL 患者和 17 例无恶性肿瘤证据的对照。lncRNA H19 被鉴定为致癌因子,在新诊断的患者中明显增加(P=0.0019,AUC=0.84),与 miR-326 呈负相关(r=-0.6,P=0.02)。此外,miR-326 的转录水平与抗凋亡 BCL-2 基因呈负相关(r=-0.6,P=0.028)。本研究中获得的新的实验和生物信息学结果可能为儿科 ALL 的分子白血病发生提供新的见解。

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