基于转录组测序分析棕榈酰转移酶DHHC7对结直肠癌侵袭的促进作用

Transcriptome sequencing‑based analysis of palmitoyltransferase DHHC7 promoting colorectal cancer invasiveness

摘要:

目的 探究棕榈酰转移酶DHHC7在结直肠癌侵袭过程中的作用及其机制。方法 敲除ZDHHC7基因的结肠癌细胞HCT116为敲除组，野生型HCT116细胞为对照组，采用转录组测序检测两组mRNA的表达情况。筛选差异表达基因，通过基因本体（Gene Ontology，GO）功能分析和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析对差异表达基因参与的功能和信号通路进行初步分析，通过Transwell侵袭实验验证DHHC7对肿瘤细胞侵袭能力的影响。结果 敲除组与对照组差异表达基因共有2 099个，其中下调基因1 190个，上调基因909个。显著富集的GO项目包括细胞黏附、细胞膜组成等。KEGG通路富集分析结果提示DHHC7可能参与细胞外基质受体相互作用和细胞黏附分子通路。Transwell实验结果证实敲除ZDHHC7可以抑制肿瘤细胞侵袭。结论 DHHC7可能通过调控细胞外基质的破坏和细胞黏附分子的表达，促进结直肠癌的侵袭。

Abstract:

Objective To explore the role and mechanism of palmitoyltransferase DHHC7 in colorectal cancer invasiveness. Methods Colorectal cancer cell lines HCT116 with ZDHHC7 knocked out were the knockout group, and wild-type HCT116 cells were the control group. The mRNA expression of the two groups was detected by transcriptome sequencing. The differentially expressed genes were screened, and the functions and signaling pathways which differentially expressed genes were involved in were preliminarily analyzed through Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and effect of DHHC7 on the invasive capacity of tumor cells was verified by Transwell invasion assay. Results There were 2 099 differentially expressed genes between the knockout group and the control group, of which 1 190 were downregulated and 909 were upregulated. Significantly enriched GO items included cell adhesion, cell membrane composition, etc.. The results of KEGG pathway enrichment analysis suggested that DHHC7 may be involved in extracelluar matrix-receptor interaction and cell adhesion molecular pathway. The result of transwell assay confirmed that ZDHHC7 knockout could inhibit the invasion of tumor cells. Conclusion DHHC7 may promote the invasiveness of colorectal cancer by regulating the destruction of extracellular matrix and the expression of cell adhesion molecules.