Hou Yiling, Wang Meng, Zhao Daqun, Liu Lu, Ding Xiang, Hou Wanru
Key Laboratory of Southwest China Wildlife Resources Conservation, College of Life Sciences, China West Normal University, Nanchong, Sichuan 637009, P.R. China.
Department of Emergency Medicine, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan 450000, P.R. China.
Oncol Lett. 2019 Feb;17(2):2507-2515. doi: 10.3892/ol.2018.9879. Epub 2018 Dec 28.
The fundamental mechanisms underlying the preventional and therapeutic effects of polysaccharides from fungi, including the immunostimulatory, antiviral and antitumor effects, are considered to occur through the modulation and stimulation of the macrophage and complement system. LDG-A, a novel polysaccharide from (L. ex Fr.) Gray exhibits marked antitumor activities . However, the underlying molecular mechanism of the antitumor activities of LDG-A remains unclear. In the present study, cell cycle analysis was performed in macrophages and B cells, and the transcriptomes of macrophages in the control group and LDG-A group were sequenced using Illumina sequencing technology to analyze the differentially expressed genes (DEGs), and elucidate the molecular mechanisms underlying the immunomodulatory and antitumor activities of LDG-A. The cell cycle analysis results indicated that LDG-A was able to promote the proliferation of B cells by promoting cell cycle progression in S phase and G/M phase and eliminating cell cycle arrest in G/G, and promote the proliferation of macrophages by promoting cell cycle progression in G/G phase and eliminating cell cycle arrest in G/M phase. Of the total number of genes (8,140), ~77.00% were expressed [reads per kilobase per million reads (RPKM) ≥1] and 1,352 genes were highly expressed (RPKM >60) in the LDG-A group. Of 775 unigenes which were identified as DEGs, 469 were downregulated and 306 genes were upregulated. A protein chip method was also used to determine the cytokines secreted by macrophages. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and GO enrichment analysis indicated that the Janus kinase/signal transducer and activator of transcription, mitogen-activated protein kinase, chemokine, vascular endothelial growth factor and transforming growth factor β signaling pathways are markedly enriched for DEGs.
真菌多糖的预防和治疗作用,包括免疫刺激、抗病毒和抗肿瘤作用,其基本机制被认为是通过调节和刺激巨噬细胞及补体系统来实现的。LDG-A是一种从灰树花(L. ex Fr.)中提取的新型多糖,具有显著的抗肿瘤活性。然而,LDG-A抗肿瘤活性的潜在分子机制仍不清楚。在本研究中,对巨噬细胞和B细胞进行了细胞周期分析,并使用Illumina测序技术对对照组和LDG-A组巨噬细胞的转录组进行测序,以分析差异表达基因(DEG),并阐明LDG-A免疫调节和抗肿瘤活性的分子机制。细胞周期分析结果表明,LDG-A能够通过促进S期和G/M期的细胞周期进程以及消除G/G期的细胞周期停滞来促进B细胞增殖,并通过促进G/G期的细胞周期进程以及消除G/M期的细胞周期停滞来促进巨噬细胞增殖。在总基因数(8140个)中,约77.00%的基因表达[每百万 reads 中每千碱基的 reads数(RPKM)≥1],且在LDG-A组中有1352个基因高表达(RPKM>60)。在被鉴定为DEG的775个单基因中,469个下调,306个基因上调。还使用蛋白质芯片方法来测定巨噬细胞分泌的细胞因子。京都基因与基因组百科全书通路富集分析和GO富集分析表明,Janus激酶/信号转导子和转录激活子、丝裂原活化蛋白激酶、趋化因子、血管内皮生长因子和转化生长因子β信号通路在DEG中显著富集。