【摘要】：旨在探索多肽9R-P201處理肝癌HepG2細(xì)胞后基因融合、單核苷酸多態(tài)性(Single nucleotide polymorphism,SNP)突變、可變剪接等事件,并分析差異表達(dá)基因所參與的生物學(xué)進(jìn)程與信號(hào)通路,以期解析多肽9R-P201在轉(zhuǎn)錄組水平對(duì)肝癌細(xì)胞的調(diào)控。通過轉(zhuǎn)錄組測序檢測9R-P201處理肝癌HepG2細(xì)胞前后基因差異表達(dá)情況,tophat-fusion軟件檢測基因融合,SAMTOOLS軟件檢測SNP位點(diǎn),r MATS軟件鑒定可變剪接,使用基因本體(Gene Ontology,GO)和京都基因與基因組百科全書(Kyoto encyclopedia of genes and genomes,KEGG)富集分析方法對(duì)差異表達(dá)基因進(jìn)行功能富集分析。結(jié)果共檢測到可變剪接事件276個(gè)、SNP位點(diǎn)5 557個(gè)、基因融合事件45個(gè);同時(shí)共得到顯著差異表達(dá)基因403個(gè),其中上調(diào)269個(gè)而下調(diào)134個(gè),基因的功能富集分析結(jié)果顯示差異表達(dá)基因顯著富集細(xì)胞生長、遷移等腫瘤相關(guān)生物進(jìn)程,并參與多條與癌癥相關(guān)的信號(hào)通路。研究表明在9R-P201誘導(dǎo)HepG2細(xì)胞后,導(dǎo)致表達(dá)差異基因顯著與腫瘤生物學(xué)進(jìn)程和通路相關(guān),并發(fā)生了大量可變剪接、SNP突變、基因融合等事件,這暗示著該多肽有望作為后續(xù)肝癌介入治療潛在藥物分子。
[Abstract]:The aim of this study was to explore gene fusion, single nucleotide polymorphism (Single nucleotide polymorphism,SNP) mutation and variable splicing after polypeptide 9R-P201 treatment of HepG2 cells, and to analyze the biological processes and signaling pathways in which differentially expressed genes were involved. The aim of this study was to elucidate the regulation of polypeptide 9R-P201 on hepatoma cells at the transcriptional level. Gene differential expression in HepG2 cells treated with 9R-P201 was detected by transcriptome sequencing, gene fusion was detected by tophat-fusion software, variable splicing was identified by, r MATS software of SNP locus detected by SAMTOOLS software, and gene ontology (Gene Ontology, was used. GO) and Kyoto gene and genome encyclopedia (Kyoto encyclopedia of genes and genomes,KEGG) enrichment analysis method for differentially expressed genes. Results A total of 276 splicing events were detected, including 5 557 SNP loci and 45 gene fusion events. A total of 403 differentially expressed genes were obtained, including 269 up-regulated genes and 134 down-regulated genes. The results of functional enrichment analysis showed that differentially expressed genes significantly enriched cell growth, migration and other tumor-related biological processes. And involved in a number of cancer-related signaling pathways. The results show that after 9R-P201 induces HepG2 cells, the differentially expressed genes are significantly associated with tumor biological processes and pathways, and a large number of events such as variable splicing, SNP mutations, gene fusion, and so on have occurred. This suggests that the polypeptide may be a potential drug molecule for subsequent interventional therapy of liver cancer.
【作者單位】： 西南交通大學(xué)生命科學(xué)與工程學(xué)院;成都市第三人民醫(yī)院病理科;
【基金】：中央高�；究蒲袠I(yè)務(wù)費(fèi)專項(xiàng)資金(2682016YXZT04) 國家大學(xué)生創(chuàng)新性實(shí)驗(yàn)計(jì)劃項(xiàng)目(201610613066)
【分類號(hào)】：R735.7
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本文編號(hào)：2328052