An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury
An inherently kidney-targeting near-infrared fluorophore based probe for early detection of acute kidney injury
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一种基于本质肾脏靶向近红外荧光团的探针，用于早期检测急性肾损伤
DOI：
10.1093/hmg/ddab021
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发表时间：
2021
影响因子：
12.6
通讯作者：
Li Xin
中科院分区：
文献类型：
--
作者：
Wang Fangqin;Jiang Xuefeng;Xiang Huaijiang;Wang Ning;Lin Weiqiang;Li Xin
在全基因组关联研究（GWAS）中发现的结直肠癌（CRC）的大多数遗传变异位于基因间区域，这意味着基因表达的致病性失调。然而，CRC中靶基因的全面评估仍有待探索。我们使用来自基因型-组织表达、癌症基因组图谱和Colonomics项目的转录组和/或DNA甲基化数据进行了多组学分析。我们为45个GWAS鉴定的变体确定了116个推定的靶基因。使用基于汇总数据的孟德尔随机化方法（SMR），我们证明了45种CRC变体中的29种可能是由基因调控的顺式效应介导的CRC易感性。在Bonferroni校正的PSMR < 0.05的临界值下，我们确定了66个推定的易感基因，包括39个以前未报道的基因。我们进一步对两个选定的基因DIP 2和SFMBT 1进行了体外分析，并提供了功能证据，表明它们通过破坏细胞行为，包括迁移，侵袭和上皮-间质转化，在结直肠癌发生中起着至关重要的作用。我们的研究揭示了大量推定的新型易感基因，并为CRC遗传风险位点的潜在机制提供了额外的见解。
Most genetic variants for colorectal cancer (CRC) identified in genome-wide association studies (GWAS) are located in intergenic regions, implying pathogenic dysregulations of gene expression. However, comprehensive assessments of target genes in CRC remain to be explored. We conducted a multi-omics analysis using transcriptome and/or DNA methylation data from the Genotype-Tissue Expression, The Cancer Genome Atlas and the Colonomics projects. We identified 116 putative target genes for 45 GWAS-identified variants. Using summary-data-based Mendelian randomization approach (SMR), we demonstrated that the CRC susceptibility for 29 out of the 45 CRC variants may be mediated bycis-effects on gene regulation. At a cutoff of the Bonferroni-correctedPSMR< 0.05, we determined 66 putative susceptibility genes, including 39 genes that have not been previously reported. We further performedin vitroassays for two selected genes,DIP2BandSFMBT1, and provide functional evidence that they play a vital role in colorectal carcinogenesis via disrupting cell behavior, including migration, invasion and epithelial–mesenchymal transition. Our study reveals a large number of putative novel susceptibility genes and provides additional insight into the underlying mechanisms for CRC genetic risk loci.