RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4.
RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4.
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DOI：
10.1155/2021/3036504
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Sun YZ
中科院分区：
文献类型：
--
作者：
Zhao Y;Huang HX;Tang SY;Sun YZ
铁皮石斛多糖（Dendrobium officinale polysaccharides，DOP）是一种治疗N-甲基-N′-硝基-N-亚硝基胍（N-methyl-N ′-nitro-N-nitrosoguanidine，MNNG-）诱导的胃癌前病变（PLGC）的有效药物。然而，根本机制尚未得到充分探讨。 我们利用RNA-Seq分析来研究可能的分子靶点，然后使用Venn软件来鉴定差异表达基因（DEG）。利用IPA软件对这些DEG进行了核心分析、上游分析和相互作用网络分析，并通过实时荧光定量PCR和Western blot对DEG进行了验证。 应用Venn软件对正常对照组（CON）、PLGC模型组（MOD）和DOP治疗组（DOP）的78个DEG进行识别。进一步的分析，这些DEG，包括核心分析，上游分析，和相互作用网络分析，进行了不相容性途径分析（IPA）。涉及的主要经典途径是SPINK 1胰腺癌途径（−log（P值）= 4.45，比率= 0.0667）和昼夜节律信号传导（−log（P值）= 2.33，比率= 0.0606）。与DOP组相比，模型组的昼夜节律信号强烈上调。预测CLOCK在上游分析中被强烈激活（z分数= 2.236）并诱导下游PER 3。此外，来自RT-PCR的7个DEG（CD 2AP、ECM 1、AQP 4、PER 3、CMTM 4、ESRRG和KCNJ 15）的相对mRNA表达水平与来自MOD与CON和MOD与DOP组的RNA-Seq数据一致。PER 3和AQP 4的基因和蛋白表达水平在PLGC模型中显著下调，并且在DOP（9.6g/kg）处理后显著升高。 这些发现不仅表明DOP通过上调PER 3和AQP 4基因和蛋白表达来抑制PLGC的发展，而且还表明其作用机制涉及调节昼夜节律信号通路。
There has been mounting evidence that Dendrobium officinale polysaccharides (DOP), a traditional Chinese medicine, are a potential candidate treatment for N-methyl-N′-nitro-N-nitrosoguanidine- (MNNG-) induced precancerous lesions of gastric cancer (PLGC). However, the underlying mechanisms have not been adequately addressed. We utilized RNA-Seq analysis to investigate possible molecular targets and then used Venn software to identify the differentially expressed genes (DEGs). Further, we analyzed these DEGs with core analysis, upstream analysis, and interaction network analysis by IPA software and validated the DEGs by real-time PCR and Western blot. 78 DEGs were identified from the normal control group (CON), the PLGC model group (MOD), and the DOP-treated group (DOP) by the Venn software. Further analysis of these DEGs, including core analysis, upstream analysis, and interaction network analysis, was performed by Ingenuity Pathway Analysis (IPA). The main canonical pathways involved were SPINK1 Pancreatic Cancer Pathway (−log (P value) = 4.45, ratio = 0.0667) and Circadian Rhythm Signaling (−log (P value) = 2.33, ratio = 0.0606). Circadian Rhythm Signaling was strongly upregulated in the model group versus the DOP group. CLOCK was predicted to be strongly activated (z-score = 2.236) in upstream analysis and induced the downstream PER3. In addition, the relative mRNA expression levels of seven DEGs (CD2AP, ECM1, AQP4, PER3, CMTM4, ESRRG, and KCNJ15) from RT-PCR agreed with RNA-Seq data from MOD versus CON and MOD versus DOP groups. The gene and protein expression levels of PER3 and AQP4 were significantly downregulated in the PLGC model and significantly increased by DOP treatment (9.6 g/kg). These findings not only showed DOP inhibits PLGC development by upregulating the PER3 and AQP4 gene and protein expression but also suggested that its mechanism of action involved modulating the Circadian Rhythm Signaling pathway.
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DOI：
10.3390/molecules26040933
发表时间：
2021-02-10
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
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通讯作者：
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影响因子：
7.4
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影响因子：
3.2
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影响因子：
16.2
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Feng, Rui-Mei;Zong, Yi-Nan;Xu, Rui-Hua
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影响因子：
3.7
作者：
Wang, Xiaoliang;Yan, Dongwang;Peng, Zhihai
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