Abstract
Purpose 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. Method 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. Result 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). Conclusions 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.
Highlights
Gastric adenocarcinoma (GAC) is a common type of digestive tract cancer worldwide, which is the third cause of cancer-related deaths
Precancerous lesions of gastric cancer (PLGC) are classified into intestinal metaplasia (IM) and dysplasia. e incidence rate of gastric cancer has been on a stable decline due to the eradication of H. pylori, improved standards of hygiene, and conscious nutrition [2]
With the guidance of traditional Chinese medicine (TCM) theory, plant natural products were the main resources for cancer chemoprevention [6], and TCM can intervene at multiple targets and levels to treat PLGC [7]
Summary
Gastric adenocarcinoma (GAC) is a common type of digestive tract cancer worldwide, which is the third cause of cancer-related deaths. It has an incidence rate and mortality rate of 10.6% (456,124 cases) and 13.6% (390,182 cases), respectively, in China in 2018 [1]. Precancerous lesions of gastric cancer (PLGC) are classified into intestinal metaplasia (IM) and dysplasia. With the guidance of traditional Chinese medicine (TCM) theory, plant natural products were the main resources for cancer chemoprevention [6], and TCM can intervene at multiple targets and levels to treat PLGC [7].
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