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精准纳米医学:载拉帕替尼壳聚糖-金纳米粒靶向 LINC01615 用于肺癌治疗。

Precision Nanomedicine: Lapatinib-Loaded Chitosan-Gold Nanoparticles Targeting LINC01615 for Lung Cancer Therapy.

机构信息

Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.

Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

出版信息

AAPS J. 2024 Nov 19;27(1):4. doi: 10.1208/s12248-024-00990-y.

DOI:10.1208/s12248-024-00990-y
PMID:39562465
Abstract

Long non-coding RNAs (lncRNAs) play essential roles as oncogenic factors in cancer progression by influencing cell proliferation, apoptosis, and metastasis pathways. This study aims to investigate the expression changes of LINC01615 in prevalent cancers, explore its correlation with patient mortality rates, and introduce a novel therapeutic approach to reduce LINC01615 expression. Using The Cancer Genome Atlas (TCGA) data, the expression changes of LINC01615 in various cancers were analyzed, and its relationship with patient survival rates through Cox regression analysis weas assessed. Co-expressed pathways related to LINC01615 were identified via network analysis. Potential drugs to decrease LINC01615 expression were identified using the GSE38376 study. Besides, chitosan-coated nanoparticles were fabricated and functionalized with the identified drug, Lapatinib, to examine their effect on lung cancer cell lines and changes in LINC01615 expression. Our results indicated elevated LINC01615 expression in various common cancers, particularly in lung cancer, which was associated with poor prognosis in lung, breast, and kidney cancers. Co-expression network analysis suggested links to metastasis-related genes. Lapatinib, identified through GEO data, was found to modulate LINC01615 expression effectively. Chitosan-gold nanoparticles conjugated with Lapatinib significantly reduced LINC01615 expression in lung cancer cell lines while enhancing apoptosis rates. Therefore, these nanoparticles could be considered a promising therapeutic candidate for treating cancers with overexpression of LINC01615.

摘要

长链非编码 RNA(lncRNA)通过影响细胞增殖、凋亡和转移途径,作为癌症进展中的致癌因子发挥重要作用。本研究旨在探讨 LINC01615 在常见癌症中的表达变化,探讨其与患者死亡率的相关性,并引入一种降低 LINC01615 表达的新治疗方法。本研究使用癌症基因组图谱(TCGA)数据分析了 LINC01615 在各种癌症中的表达变化,并通过 Cox 回归分析评估了其与患者生存率的关系。通过网络分析确定了与 LINC01615 相关的共表达途径。使用 GSE38376 研究确定了降低 LINC01615 表达的潜在药物。此外,还制备了壳聚糖包覆的纳米颗粒,并对其进行了功能化,使其与鉴定出的药物拉帕替尼(Lapatinib)结合,以检测其对肺癌细胞系的影响和 LINC01615 表达的变化。结果表明,LINC01615 在各种常见癌症中表达升高,尤其是在肺癌中,与肺癌、乳腺癌和肾癌的不良预后相关。共表达网络分析表明与转移相关基因有关。通过 GEO 数据鉴定出的拉帕替尼可有效调节 LINC01615 的表达。壳聚糖-金纳米颗粒与拉帕替尼偶联可显著降低肺癌细胞系中的 LINC01615 表达,同时提高细胞凋亡率。因此,这些纳米颗粒可以被认为是治疗 LINC01615 过表达癌症的一种很有前途的治疗候选物。

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本文引用的文献

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Theranostics. 2024 Jul 2;14(10):4127-4146. doi: 10.7150/thno.97768. eCollection 2024.
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Biosynthesized BiFeO@Ag nanoparticles mediated Scenedesmus obliquus induce apoptosis in AGS gastric cancer cell line.生物合成的 BiFeO@Ag 纳米颗粒介导的斜生栅藻诱导 AGS 胃癌细胞系凋亡。
Sci Rep. 2024 May 4;14(1):10284. doi: 10.1038/s41598-024-57157-0.
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Therapeutic effects of guanidine hydrochloride on breast cancer through targeting KCNG1 gene.
盐酸胍通过靶向 KCNG1 基因对乳腺癌的治疗作用。
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Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.巨噬细胞 M2 极化参与了拉帕替尼介导的肺癌化学预防作用。
Biomed Pharmacother. 2023 May;161:114527. doi: 10.1016/j.biopha.2023.114527. Epub 2023 Mar 15.
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Fabrication of a Dual-Drug-Loaded Smart Niosome-g-Chitosan Polymeric Platform for Lung Cancer Treatment.用于肺癌治疗的双药负载智能脂质体-g-壳聚糖聚合物平台的制备
Polymers (Basel). 2023 Jan 6;15(2):298. doi: 10.3390/polym15020298.
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