通过RNA-seq探究外源性硫化氢对肝癌细胞系HepG2的影响

Exploring the effects of exogenous hydrogen sulfide on hepatoma cell line HepG2 by RNA-seq

目的探究外源性硫化氢(hydrogen sulfide,H 2S)对肝细胞癌(hepatocellular carcinoma,HCC)的影响及可能的分子机制,为HCC诊疗提供理论实验支持。方法从GEO数据库中获取HCC的基因表达数据,并筛选外源性H 2S处理HepG2细胞的RNA-seq数据,通过差异基因筛选、GO和KEGG通路分析,确定H 2S调控的主要生物学功能和信号通路。结果数据分析表明,与正常组织相比,肝癌组织中硫化氢合成关键酶胱硫醚γ裂解酶(cystathionine γ-lyase,CSE)和胱硫醚合成酶(cystathionine β-synthase,CBS)的表达显著下降。筛选出3640个差异基因,其中317个与细胞衰老、580个与细胞增殖、43个与凋亡相关。通过蛋白互作网络分析,Jun、MAPK1和MAPK3等关键基因被识别,提示H 2S可能通过调控Jun/MAPK信号通路影响HCC的发生发展。结论H 2S在HCC中可能通过Jun/MAPK通路发挥的调控作用,为H 2S在HCC中的分子机制研究和潜在治疗应用提供了基础。

Objective To investigate the effects of exogenous hydrogen sulfide(H 2S)on HCC and the possible molecular mechanisms,and to provide experimental support for the diagnosis and treatment of HCC.Methods Gene expression data of HCC were obtained from the GEO database.Transcriptomic data(RNA-seq)of HepG2 cells treated with exogenous H 2S were analyzed to identify differentially expressed genes(DEGs).GO and KEGG pathway enrichment analyses were conducted to explore the main biological functions and pathways associated with these DEGs.Results GEO analysis revealed that the expression levels of key H 2S-producing enzymes,cystathionineγ-lyase(CSE)and cystathionineβ-synthase(CBS),were significantly reduced in HCC tissues compared to normal tissues.A total of 3640 DEGs were identified,among which 317 were related to cellular senescence,580 to cell proliferation,and 43 to apoptosis.Protein-protein interaction network analysis highlighted Jun,MAPK1 and MAPK3 as key genes,suggesting that the effects of H 2S on HCC may be associated with the Jun/MAPK signaling pathway.Conclusion H 2S may regulate HCC development through the Jun/MAPK pathway,offering a basis for further exploration of H 2S in the molecular mechanisms and potential therapeutic applications in HCC.