MicroRNA-Based Discovery of Biomarkers, Therapeutic Targets, and Repositioning Drugs for Breast Cancer.
MicroRNA-Based Discovery of Biomarkers, Therapeutic Targets, and Repositioning Drugs for Breast Cancer.
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DOI：
10.3390/cells12141917
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发表时间：
2023-07-23
期刊：
影响因子：
6
通讯作者：
Guo, Nancy Lan
中科院分区：
文献类型：
--
作者：
Ye, Qing;Raese, Rebecca A.;Luo, Dajie;Feng, Juan;Xin, Wenjun;Dong, Chunlin;Qian, Yong;Guo, Nancy Lan
关键词：
早期发现和个体化治疗的生物标记物可以提高乳腺癌的治疗水平。用86个microRNAs(MiRNAs)来区分乳腺癌和正常乳腺组织(n=52)，总体准确率为90.4%。与正常对照相比，有6个miRNAs在肿瘤和乳腺癌患者血液中表达一致。12个miRNAs在肿瘤、正常乳腺组织和患者生存期(n=1093)中表达一致，其中7个是潜在的肿瘤抑制因子，5个是潜在的肿瘤抑制因子。从这86个miRNAs的实验验证的靶基因中，筛选出与NCCN推荐的19种乳腺癌药物的体外药物反应相关的泛敏感和泛耐药基因，这些基因具有一致的mRNA和蛋白表达。结合CRISPR-Cas9/RNAi体外增殖分析和患者生存分析，MEK抑制剂PD19830和BRD-K12244279、匹罗卡品和特莫林被发现为治疗乳腺癌的潜在新药选择。使用人类乳腺癌细胞系鉴定了对所发现的药物做出反应的多组学生物标志物。这项研究展示了一条基于miRNA的人工智能管道，发现可应用于多种癌症类型的生物标记物、治疗靶点和重新定位药物。
Breast cancer treatment can be improved with biomarkers for early detection and individualized therapy. A set of 86 microRNAs (miRNAs) were identified to separate breast cancer tumors from normal breast tissues (n = 52) with an overall accuracy of 90.4%. Six miRNAs had concordant expression in both tumors and breast cancer patient blood samples compared with the normal control samples. Twelve miRNAs showed concordant expression in tumors vs. normal breast tissues and patient survival (n = 1093), with seven as potential tumor suppressors and five as potential oncomiRs. From experimentally validated target genes of these 86 miRNAs, pan-sensitive and pan-resistant genes with concordant mRNA and protein expression associated with in-vitro drug response to 19 NCCN-recommended breast cancer drugs were selected. Combined with in-vitro proliferation assays using CRISPR-Cas9/RNAi and patient survival analysis, MEK inhibitors PD19830 and BRD-K12244279, pilocarpine, and tremorine were discovered as potential new drug options for treating breast cancer. Multi-omics biomarkers of response to the discovered drugs were identified using human breast cancer cell lines. This study presented an artificial intelligence pipeline of miRNA-based discovery of biomarkers, therapeutic targets, and repositioning drugs that can be applied to many cancer types.
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影响因子：
4.8
作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/j.vascn.2008.10.003
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作者：
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影响因子：
3.8
作者：
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