DNMT1/miR-152-3p/SOS1 信号轴促进非小细胞肺癌干细胞的自我更新和肿瘤生长

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY
Qing Yuan, Rubo Wang, Xiang Li, Fei Sun, Jiazhi Lin, Zhimin Fu, Jiansong Zhang
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引用次数: 0

摘要

CSLCs(癌症干细胞样细胞)是肿瘤发生的核心,受到表观遗传修饰的内在影响。本研究旨在阐明 DNMT1/miR-152-3p/SOS1 轴调控 LCSLCs(肺癌干细胞样细胞)自我更新和肿瘤生长的内在机制。使用 TargetScan Human 8.0 预测了 miR-152-3p 的靶基因。在悬浮培养的非小细胞肺癌(NSCLC)细胞系 H460 和 A549 细胞衍生的球状细胞中比较了 LCSLC 的自我更新和肿瘤生长。通过体外和体内功能增益实验评估了 DNMT1/miR-152-3p/SOS1 轴的功能效应。此外,我们还采用荧光素酶报告实验来分析 DNMT1、miR-152-3p 和 SOS1 之间的相互作用。我们的研究结果表明,DNMT1 和 miR-152-3p 之间存在负相互作用,导致 miR-152-3p 水平降低。这反过来又会导致 miR-152-3p 对靶基因 SOS1 的抑制作用减弱,最终激活 SOS1,并在 LCSLC 的自我更新和肿瘤生长中发挥重要作用。然而,SOS1 的改变并不影响 DNMT1/miR-152-3p 的调控。因此,有理由推断 DNMT1/miR-152-3p 负反馈环通过 SOS1 关键性地维持了 LCSLC 的自我更新和肿瘤生长。这项研究揭示了NSCLC中CSLC(癌症干细胞)自我更新和肿瘤生长的新机制,并确定了NSCLC治疗的潜在靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
DNMT1/miR-152-3p/SOS1 signaling axis promotes self-renewal and tumor growth of cancer stem-like cells derived from non-small cell lung cancer
CSLCs(Cancer stem cell-like cells), which are central to tumorigenesis, are intrinsically influenced by epigenetic modifications. This study aimed to elucidate the underlying mechanism involving the DNMT1/miR-152-3p/SOS1 axis in regulating the self-renewal and tumor growth of LCSLCs (lung cancer stem-like cells). Target genes of miR-152-3p were predicted using TargetScan Human 8.0. Self-renewal and tumor growth of LCSLC were compared in suspension-cultured non-small cell lung cancer (NSCLC) cell lines H460 and A549 cell-derived globe cells. Functional effects of the DNMT1/miR-152-3p/SOS1 axis were assessed through gain-of-function experiments in vitro and in vivo. Additionally, luciferase reporter assays were employed to analyze the interaction among DNMT1, miR-152-3p, and SOS1. Our findings highlight a negative interaction between DNMT1 and miR-152-3p, resulting in reduced miR-152-3p level. This, in turn, leads to the alleviation of the inhibitory effect of miR-152-3p on the target gene SOS1, ultimately activating SOS1 and playing an essential role in self-renewal and tumor growth of LCSLC. However, the alteration of SOS1 does not affect DNMT1/miR-152-3p regulation. Therefore, it is reasonable to infer that the DNMT1/miR-152-3p negative feedback loop critically sustains self-renewal and tumor growth of LCSLC through SOS1. This study reveals a novel mechanism underpinning self-renewal and tumor growth of CSLC (cancer stem cell) in NSCLC and identifies potential therapeutic targets for NSCLC treatment.
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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