Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer

Chen, Yang; Gao, Yun; Yi, Xiaojiao; Zhang, Jinghui; Chen, Zhongjian; Wu, Yao

doi:10.3389/fphar.2020.544647

Cited by 14 publications

(5 citation statements)

References 31 publications

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“…We found three key targets (ABCG5, HMGCR, SULT2A1) and one pathway (bile secretion). Integration of metabolomics and transcriptomics was designed to study the metabolite profiles and gene expression profiles in biological systems under administration conditions and analyze the internal changes of biological systems from two levels ( Chen et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

et al. 2023

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Background: Intrahepatic cholestasis (IC) is a disorder of bile production, secretion, and excretion with various causes. Crocin I (CR) is effective in the treatment of IC, but its underlying mechanisms need to be further explored. We aimed to reveal the therapeutic mechanism of crocin I for IC by combining an integrated strategy of metabolomics and transcriptomics.Methods: The hepatoprotective effect of CR against cholestasis liver injury induced by α-naphthylisothiocyanate (ANIT) was evaluated in rats. The serum biochemical indices, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bile acid (TBA), total bilirubin (TBIL), direct bilirubin (DBIL), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 1β (IL-1β), as well as the liver oxidative stress indexes and the pathological characteristics of the liver were analyzed. In addition, we also performed a serum metabolomics study using UPLC-Q Exactive HF-X technology to investigate the effect of CR on the serum of rats with ANIT-induced IC and screened potential biomarkers. The enrichment analysis of differential expressed genes (DEGs) was performed by transcriptomics. Finally, the regulatory targets of CR on potential biomarkers were obtained by combined analysis, and the relevant key targets were verified by western blotting.Results: CR improved serum and liver homogenate indexes and alleviated liver histological injury. Compared with ANIT group, the CR group had 76 differential metabolites, and 10 metabolic pathways were enriched. There were 473 DEGs significantly changed after CR treatment, most of which were enriched in the retinol metabolism, calcium signaling pathway, PPAR signaling pathway, circadian rhythm, chemokine signaling pathway, arachidonic acid metabolism, bile secretion, primary bile acid biosynthesis, and other pathways. By constructing the “compound-reaction-enzyme-gene” interaction network, three potential key-target regulation biomarkers were obtained, including 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), ATP-binding cassette transporter G5 (ABCG5), and sulfotransferase2A1(SULT2A1), which were further verified by western blotting. Compared with the ANIT group, the CR group significantly increased the expression of ABCG5 and SULT2A1, and the expression of HMGCR significantly decreased.Conclusion: Combined metabolomic and transcriptomic analyses show that CR has a therapeutic effect on IC through regulation of the biosynthesis of bile acids and bilirubin in the bile secretion pathway and regulation of the expression of HMGCR, ABCG5, and SULT2A1.

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Section: Discussionmentioning

confidence: 99%

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

et al. 2023

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“…. Chen et al (2020c) combined metabolomics and transcriptomics to assess the anti-cancer activity of shikonin in human CRC cells. They showed that shikonin exhibits significant anti-tumor activity and that the regulation of purine metabolism may contribute to the anti-cancer effects of shikonin.…”

Section: Transcriptomicsmentioning

confidence: 99%

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers

Wang

et al. 2022

Front. Pharmacol.

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Chinese herbal medicines offer a rich source of anti-cancer drugs. Differences between the pharmacology of Chinese herbal medicines and modern synthetic chemicals hinder the development of drugs derived from herbal products. To address this challenge, novel omics approaches including transcriptomics, proteomics, genomics, metabolomics, and microbiomics have been applied to dissect the pharmacological benefits of Chinese herbal medicines in cancer treatments. Numerous Chinese herbal medicines have shown potential anti-tumor effects on different gastrointestinal (GI) cancers while eliminating the side effects associated with conventional cancer therapies. The present study aimed to provide an overview of recent research focusing on Chinese herbal medicines in GI cancer treatment, based on omics approaches. This review also illustrates the potential utility of omics approaches in herbal-derived drug discovery. Omics approaches can precisely and efficiently reveal the key molecular targets and intracellular interaction networks of Chinese herbal medicines in GI cancer treatment. This study summarizes the application of different omics-based approaches in investigating the effects and mechanisms of Chinese herbal medicines in GI cancers. Future research directions are also proposed for this area of study.

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“…Additionally, the effects of shikonin on the survival and tumor growth of the nude mice model, as well as the migration and invasion of human CRC cells, appear to be able to imply the fact that shikonin inhibited the metastasis of CRC through SIRT2- (silent information regulators 2-) mediated antitumor effect ( Zhang et al, 2017b ). Furthermore, the anti-CRC activity of shikonin was also validated by the approaches of metabolomics, transcriptomics, and proteomics ( Chen et al, 2020c ; Chen et al, 2020d ). In short, shikonin is a potentially effective agent for the treatment of CRC, which has attention-grabbing clinical application and research value.…”

Section: Antitumor Status Of Traditional Chinese Medicine and Its Clinical Trials On Colorectal Cancermentioning

confidence: 99%

Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery

Sun

Zhang

et al. 2021

Front. Pharmacol.

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As an important part of complementary and alternative medicine, traditional Chinese medicine (TCM) has been applied to treat a host of diseases for centuries. Over the years, with the incidence rate of human colorectal cancer (CRC) increasing continuously and the advantage of TCM gradually becoming more prominent, the importance of TCM in both domestic and international fields is also growing with each passing day. However, the unknowability of active ingredients, effective substances, and the underlying mechanisms of TCM against this malignant tumor greatly restricts the translation degree of clinical products and the pace of precision medicine. In this review, based on the characteristics of TCM and the oral administration of most ingredients, we herein provide beneficial information for the clinical utilization of TCM in the prevention and treatment of CRC and retrospect the current preclinical studies on the related active ingredients, as well as put forward the research mode for the discovery of active ingredients and effective substances in TCM, to provide novel insights into the research and development of innovative agents from this conventional medicine for CRC treatment and assist the realization of precision medicine.

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Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism Underlying Shikonin in Colon Cancer

Cited by 14 publications

References 31 publications

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

Mechanism of crocin I on ANIT-induced intrahepatic cholestasis by combined metabolomics and transcriptomics

Using omics approaches to dissect the therapeutic effects of Chinese herbal medicines on gastrointestinal cancers

Traditional Chinese Medicine and Colorectal Cancer: Implications for Drug Discovery

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