Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2

Abstract

Euphorbia factors, lathyrane-type diterpenoids isolated from the medical herb Euphorbia lathyris L. (Euphorbiaceae), have been associated with intestinal irritation toxicity, but the mechanisms underlying this phenomenon are still unknown. The objective of this study was to evaluate the transcriptome and miRNA profiles of human colon adenocarcinoma Caco-2 cells in response to Euphorbia factors L1 (EFL1) and EFL2. Whole transcriptomes of mRNA and microRNA (miRNA) were obtained using second generation high-throughput sequencing technology in response to 200 μM EFL treatment for 72 h, and the differentially expressed genes and metabolism pathway were enriched. Gene structure changes were analyzed by comparing them with reference genome sequences. After 72 h of treatment, 16 miRNAs and 154 mRNAs were differently expressed between the EFL1 group and the control group, and 47 miRNAs and 1101 mRNAs were differentially expressed between the EFL2 group and the control. Using clusters of orthologous protein enrichment, the sequenced mRNAs were shown to be mainly involved in transcription, post-translational modification, protein turnover, chaperones, signal transduction mechanisms, intracellular trafficking, secretion, vesicular transport, and the cytoskeleton. The differentially expressed mRNA functions and pathways were enriched in transmembrane transport, T cell extravasation, the IL-17 signaling pathway, apoptosis, and the cell cycle. The differentially expressed miRNA EFLs caused changes in the structure of the gene, including alternative splicing, insertion and deletion, and single nucleotide polymorphisms. This study reveals the underlying mechanism responsible for the toxicity of EFLs in intestinal cells based on transcriptome and miRNA profiles of gene expression and structure.

Combined transcriptomic and proteomic analysis reveals the mechanism of Xing-Qi-Huo-Xue granules on BLM-induced pulmonary fibrosis in rats

“…Many studies utilized transcriptomics and proteomics techniques 19,20 , to investigate the speci c mechanisms of natural herbs or extracts in disease. Due to the heterogeneity of the transcriptome and proteome, the combination of the two is increasingly recognized as a promising approach to studying the therapeutic mechanisms of natural herbal extracts 21 . In this study, differentially expressed genes and proteins were initially identi ed following BLM stimulation and XQHX intervention.…”

Nuciferine Effectively Protects Mice against Acetaminophen-Induced Liver Injury

“…We then downloaded the 2D structure of Nuci from the PubChem database (https://pubchem.ncbi.nlm.nih.gov/, accessed on 5 October 2022) and imported it into Chem3D software (Waltham, MA, USA) to convert it into a 3D structure, according to the principle of energy minimization [25]. The semi-flexible docking method in Surflex-Dock GeomX mode was used in the docking between proteins and Nuci [26]. The total score of docking is a comprehensive factor to evaluate polar complementarity, hydrophobic complementarity, entropy, and solvation.…”