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差异表达 microRNAs 在 PEG 化脂质体包裹的 Re 介导的抑制原位下咽肿瘤中的作用。

Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor.

机构信息

Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, No. 155, Sec. 2, Linong St. Beitou District, Taipei 11221, Taiwan.

Department of Nuclear Medicine, Far Eastern Memorial Hospital, New Taipei City 22000, Taiwan.

出版信息

Molecules. 2020 Aug 8;25(16):3609. doi: 10.3390/molecules25163609.

DOI:10.3390/molecules25163609
PMID:32784458
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7463599/
Abstract

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by Re-liposome. Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.

摘要

下咽癌(HPC)是头颈部癌症(HNSCC)中生存率最低的一种。然而,HPC 的治疗方法仍需进一步研究。本研究制备了一种治疗下咽癌的诊断和治疗一体化的 Re-liposome,并分析了失调的 microRNA 表达谱。通过生物发光成像和下一代测序(NGS)分析评估 Re-liposome 对 HPC 肿瘤的治疗效果,以解决失调的 microRNAs 及其相关信号通路。还使用临床 HNSCC 样本和癌症基因组图谱(TCGA)数据库中的临床信息对差异表达的 microRNAs 进行了验证。给荷瘤小鼠重复给予 Re-liposome 剂量,治疗后肿瘤生长明显受到抑制。对于 NGS 分析,当倍数变化的截止值设定为 5 时,分别有 13 个和 9 个 microRNAs 分别上调和下调。此外,miR-206-3p 和 miR-142-5p 分别是上调和下调倍数最高的 microRNAs。根据人类癌症差异表达 microRNAs(dbDEMC)分析,Re-liposome 上调的 microRNAs 大多为肿瘤抑制因子,而下调的 microRNAs 为致癌 microRNAs。KEGG 通路分析表明,癌症相关通路和嗅觉和味觉转导是受 Re-liposome 影响最大的通路。Re-liposome 下调的 microRNAs,包括 miR-143、miR-6723、miR-944 和 miR-136,与高表达水平下较低的生存率相关。Re-liposome 可以抑制体内 HPC 肿瘤,治疗效果与 microRNA 的失调有关,microRNA 可作为预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/5f36f6ba525d/molecules-25-03609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/fcdd9712e2bd/molecules-25-03609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/7200228f5d5b/molecules-25-03609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/c688f75a2939/molecules-25-03609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/e20bfa6b5192/molecules-25-03609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/c957a876968e/molecules-25-03609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/364bf209daf6/molecules-25-03609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/5f36f6ba525d/molecules-25-03609-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/fcdd9712e2bd/molecules-25-03609-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/7200228f5d5b/molecules-25-03609-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/c688f75a2939/molecules-25-03609-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/e20bfa6b5192/molecules-25-03609-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/c957a876968e/molecules-25-03609-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/364bf209daf6/molecules-25-03609-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c2b2/7463599/5f36f6ba525d/molecules-25-03609-g007.jpg

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