[關(guān)鍵詞]
[摘要]
目的 探討千層紙素A抑制宮頸癌的作用及潛在機(jī)制。方法 在GEO和TCGA數(shù)據(jù)集中分析SHC SH2結(jié)構(gòu)域結(jié)合蛋白1(SHCBP1)在宮頸癌患者與健康人之間的表達(dá)的差異;通過MTT實(shí)驗(yàn)驗(yàn)證千層紙素A對(duì)HeLa細(xì)胞的抑制作用。采用Western blotting實(shí)驗(yàn)對(duì)千層紙素A與SHCBP1之間關(guān)系進(jìn)行研究,運(yùn)用分子模擬對(duì)接評(píng)估千層紙素A與SHCBP1蛋白的對(duì)接效果;Linkedomics分析宮頸癌患者中SHCBP1的共表達(dá)基因;基因本體(GO)和京都基因組百科全書(KEGG)分析相關(guān)共表達(dá)基因的潛在機(jī)制;CIBERSORT法分析SHCBP1與宮頸癌免疫細(xì)胞浸潤(rùn)的相關(guān)性;TISIDB數(shù)據(jù)庫(kù)分析SHCBP1與免疫檢查點(diǎn)的關(guān)系。結(jié)果 GEO數(shù)據(jù)庫(kù)及TCGA數(shù)據(jù)庫(kù)的分析結(jié)果得出,SHCBP1在宮頸癌患者中顯著高表達(dá);MTT和Western blotting分析結(jié)果顯示,千層紙素A在10 μmol/L即對(duì)HeLa細(xì)胞增殖和SHCBP1的表達(dá)具有顯著的抑制效果(P<0.05)。分子對(duì)接結(jié)果顯示,千層紙素A與SHCBP1具有較好的結(jié)合勢(shì)能;TISIDB數(shù)據(jù)庫(kù)的研究及CIBERSORT法對(duì)GEO數(shù)據(jù)集的分析結(jié)果得出,SHCBP1參與了宮頸癌細(xì)胞的免疫浸潤(rùn);SHCBP1及其共表達(dá)基因主要富集于炎癥相關(guān)途徑中。結(jié)論 千層紙素A通過抑制SHCBP1介導(dǎo)的免疫浸潤(rùn)來(lái)抑制宮頸癌的生長(zhǎng),這可能在宮頸癌的治療中有重要意義。
[Key word]
[Abstract]
Objective To investigate the inhibitory effect and potential mechanism of oroxylin A on cervical cancer. Methods The expression difference of SHCBP1 between cervical cancer patients and healthy people was analyzed in GEO and TCGA datasets. The inhibitory effect of oroxylin A on Hela cells was verified by MTT assay. Western blotting experiments were used to study the relationship between oroxylin A and SHCBP1, and molecular simulation docking was used to evaluate the docking effect between oroxylin A and SHCBP1. The co-expression gene of SHCBP1 in patients with cervical cancer was analyzed by Linkedomics. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) were used to analyze the underlying mechanisms of related co-expressed genes. CIBERSORT method was used to analyze the correlation between SHCBP1 and immune cell infiltration of cervical cancer. TISIDB database was used to analyze the relationship between SHCBP1 and immune checkpoint. Results The analysis results of GEO database and TCGA database showed that SHCBP1 was highly expressed in cervical cancer patients. The results of MTT and Western blotting analysis showed that oroxylin A had significant inhibitory effect on the expression of Hela cells and SHCBP1 at the concentration of 10 μmol/L (P< 0.05). The results of molecular docking showed that the combination of oroxylin A and SHCBP1 had good potential energy. The results of TISIDB database and CIBERSORT analysis of GEO data show that SHCBP1 is involved in the immune invasion of cervical cancer cells. SHCBP1 and its co-expression genes are mainly enriched in inflammatory pathways. Conclusion Oroxylin A suppresses the growth of cervical cancer by suppressing SHCBP1-mediated immune infiltration, which could potentially have significant implications in the treatment of cervical cancer.
[中圖分類號(hào)]
R285;R979.1
[基金項(xiàng)目]