A Novel Regulatory Network of Noncoding RNAs in the Cadmium-Induced Malignant Transformation of Human Bronchial Epithelial Cells.

IF 2.7 4区 医学 Q3 TOXICOLOGY
Yueqing Shao, Pengya Zhao, Linlin Wang, Yanfang Yang, Lihua Huang
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引用次数: 0

Abstract

Long-term exposure to cadmium (Cd) is closely linked to an increased risk of lung cancer, yet the underlying mechanisms driving this malignant transformation remain elusive. Noncoding RNAs may hold the key to understanding the complex pathways involved in cadmium-induced carcinogenesis. This study reveals a novel regulatory network involving circ_000877, lnc237177, and miR-3192-5p, which targets cyclin-D1(CCND1) and matrix metalloproteinase 2 (MMP-2), thereby promoting the Cd-induced malignant transformation of human bronchial epithelial (16HBE) cells. Utilizing an established 16HBE malignant transformation model induced by Cd exposure, RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that both circ_000877 and lnc237177 were significantly upregulated. Functional assays further confirmed the roles of these molecules in facilitating malignant transformation. Mechanistically, circ_000877 and lnc237177 collaboratively targeted miR-3192-5p, thereby modulating both mRNA and protein expression levels of cyclin-D1 and MMP-2. Collectively, this study offers novel perspectives into the mechanism through which circRNA and lncRNA jointly regulate miRNA in a crosstalk network during Cd-induced malignant transformation, thereby enhancing our understanding of cadmium's toxicological impact.

镉诱导人支气管上皮细胞恶性转化的非编码rna新调控网络。
长期接触镉(Cd)与肺癌风险增加密切相关,但驱动这种恶性转化的潜在机制仍然难以捉摸。非编码rna可能是理解镉诱导癌变的复杂途径的关键。本研究揭示了一个涉及circ_000877、lnc237177和miR-3192-5p的新的调控网络,其靶向细胞周期蛋白d1 (CCND1)和基质金属蛋白酶2 (MMP-2),从而促进cd诱导的人支气管上皮(16HBE)细胞的恶性转化。利用建立的镉暴露诱导16HBE恶性转化模型,RNA测序和定量实时聚合酶链反应(qRT-PCR)分析表明circ_000877和lnc237177均显著上调。功能分析进一步证实了这些分子在促进恶性转化中的作用。在机制上,circ_000877和lnc237177协同靶向miR-3192-5p,从而调节cyclin-D1和MMP-2的mRNA和蛋白表达水平。总的来说,本研究为cd诱导恶性转化过程中circRNA和lncRNA在串扰网络中共同调控miRNA的机制提供了新的视角,从而增强了我们对镉毒理学影响的理解。
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来源期刊
CiteScore
7.00
自引率
6.10%
发文量
145
审稿时长
1 months
期刊介绍: Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.
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