Transcriptomics and experimental validation-based approach to understand the effect and mechanism of Huangqin tang interfeience with colitis associated colorectal cancer

Abstract

ContextChronic inflammation is usually caused by persistent irritation or uncontrolled infection and is characterized by ongoing tissue damage, injury-induced cellular proliferation and tissue repair. Colitis-associated colorectal cancer (CAC) isone of the classic examples of tumors that are tightly related to chronic inflammation. BackgroundTo investigated the key pharmacodynamic genes of HQT interventions in CAC by using transcriptome predictions and experiments.Materials & Methods: We used the azoxymethane/dextran sodium sulfate method to induce the mice CAC model. After preventive administration of HQT to the mice model, colonic tissues were taken for transcriptome sequencing and the transcriptome results were then experimentally validated using quantitative Real-Time PCR technique. ResultsTranscriptome sequencing revealed that the effect of the mechanism of HQT on the CAC mice model maybe related to its inhibition of accelerated epithelial mesenchymal transition and induction of pyroptosis. The levels of Matrix-metalloproteinases such as MMP-2, MMP-9 were significantly reduced in CAC mice treated with HQT; The mRNA expression for Krt17, App, CD44 and WNT pathway related sites such as Lrrc15, Cldn-1, Mpc1, Agr2 which are related factors affecting the epithelial mesenchymal transition were significantly reduced in CAC mice treated with HQT; the aberrant mRNA expression of inflammasome components that drive pyroptosis, including Nlrp3, Caspase-1, ASC, GSDMD and its mediated product IL-18 have been improved. ConclusionsOur findings provide preliminary clarification that inhibiting the progression of CAC by using HQT is effective, the mechanism of action may be relatedto the inhibition of epithelial mesenchymal transition and induction of pyroptosis during tumorigenesis.