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

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 transcriptom...

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Autores principales: Zou, Lingyue, Bao, Wenqiang, Gao, Yadong, Chen, Mengting, Wu, Yajiao, Wang, Shuo, Li, Chutao, Zhang, Jian, Zhang, Dongcheng, Wang, Qi, Zhu, An
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608949/
https://www.ncbi.nlm.nih.gov/pubmed/36296525
http://dx.doi.org/10.3390/molecules27206931
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author Zou, Lingyue
Bao, Wenqiang
Gao, Yadong
Chen, Mengting
Wu, Yajiao
Wang, Shuo
Li, Chutao
Zhang, Jian
Zhang, Dongcheng
Wang, Qi
Zhu, An
author_facet Zou, Lingyue
Bao, Wenqiang
Gao, Yadong
Chen, Mengting
Wu, Yajiao
Wang, Shuo
Li, Chutao
Zhang, Jian
Zhang, Dongcheng
Wang, Qi
Zhu, An
author_sort Zou, Lingyue
collection PubMed
description 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.
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spelling pubmed-96089492022-10-28 Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2 Zou, Lingyue Bao, Wenqiang Gao, Yadong Chen, Mengting Wu, Yajiao Wang, Shuo Li, Chutao Zhang, Jian Zhang, Dongcheng Wang, Qi Zhu, An Molecules Article 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. MDPI 2022-10-16 /pmc/articles/PMC9608949/ /pubmed/36296525 http://dx.doi.org/10.3390/molecules27206931 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zou, Lingyue
Bao, Wenqiang
Gao, Yadong
Chen, Mengting
Wu, Yajiao
Wang, Shuo
Li, Chutao
Zhang, Jian
Zhang, Dongcheng
Wang, Qi
Zhu, An
Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title_full Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title_fullStr Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title_full_unstemmed Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title_short Integrated Analysis of Transcriptome and microRNA Profile Reveals the Toxicity of Euphorbia Factors toward Human Colon Adenocarcinoma Cell Line Caco-2
title_sort integrated analysis of transcriptome and microrna profile reveals the toxicity of euphorbia factors toward human colon adenocarcinoma cell line caco-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608949/
https://www.ncbi.nlm.nih.gov/pubmed/36296525
http://dx.doi.org/10.3390/molecules27206931
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