Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment

Manka, Paul; Coombes, Jason D.; Boosman, R.; Gauthier, Karine; Papa, Salvatore; Syn, Wing Kin

doi:10.1016/j.canlet.2018.01.055

Cited by 23 publications

(15 citation statements)

References 109 publications

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“…In the present study, the hub targets of SHL oral liquid also enriched in the pathways related to cancer, including colorectal cancer, breast cancer, and thyroid hormone signaling pathway. Thyroid hormone signaling pathway was reported to involve several mechanisms to activate either the tumor cells or cells of the micro-environment, but the mechanisms were unclear [69,70]. These findings showed that the ingredients of SHL oral liquid might have potency for anti-tumor activity.…”

Section: Discussionmentioning

confidence: 95%

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

Zhuang

Wen

Zhang

et al. 2020

European Journal of Integrative Medicine

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Introduction: Shuanghuanglian (SHL) oral liquid is a well-known traditional Chinese medicine preparation administered for respiratory tract infections in China. However, the underlying pharmacological mechanisms remain unclear. The present study aims to determine the potential pharmacological mechanisms of SHL oral liquid based on network pharmacology. Methods: A network pharmacology-based strategy including collection and analysis of putative compounds and target genes, network construction, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and Gene Ontology (GO) enrichment, identification of key compounds and target genes, and molecule docking was performed in this study. Results: A total of 82 bioactive compounds and 226 putative target genes of SHL oral liquid were collected. Of note, 28 hub target genes including 4 major hub target genes: estrogen receptor 1 (ESR1), nuclear receptor coactivator 2 (NCOA2), nuclear receptor coactivator 1 (NCOA1), androgen receptor (AR) and 5 key compounds (quercetin, luteolin, baicalein, kaempferol and wogonin) were identified based on network analysis. The hub target genes mainly enriched in pathways including PI3K-Akt signaling pathway, human cytomegalovirus infection, and human papillomavirus infection, which could be the underlying pharmacological mechanisms of SHL oral liquid for treating diseases. Moreover, the key compounds had great molecule docking binding affinity with the major hub target genes. Conclusion: Using network pharmacology analysis, SHL oral liquid was found to contain anti-virus, anti-inflammatory, and "multi-compounds and multi-targets" with therapeutic actions. These findings may provide a valuable direction for further clinical application and research. 1. Background SHL oral liquid is a well-known traditional Chinese medicine preparation frequently applied to treat acute upper respiratory tract infection, acute bronchitis, and pneumonia [1]. SHL oral liquid is derived from three Chinese medicinal herbs, namely, Flos Lonicerae (Jinyinhua, JYH), Radix Scutellariae (Huangqin, HQ), and Fructus Forsythiae (Lianqiao, LQ), which were officially recorded in the Chinese

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Section: Discussionmentioning

confidence: 95%

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

Zhuang

Wen

Zhang

et al. 2020

European Journal of Integrative Medicine

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“…Furthermore, SMARCA2 is involved in the same pathway as our next suggestively associated locus, IGF1R. They both belong to hepatocellular carcinoma (HCC) pathway that has in turn been associated with abnormal thyroid hormone signaling 62 further linking our genetic variants with thyroid dysfunction. IGF1R has pleiotropic roles in humans, among which two roles are relevant for our study.…”

Section: Discussionmentioning

confidence: 74%

AATF and SMARCA2 are associated with thyroid volume in Hashimoto’s thyroiditis patients

Brčić

Barić

Benzon

et al. 2020

Sci Rep

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Thyroid volume of Hashimoto's thyroiditis (HT) patients varies in size over the course of disease and it may reflect changes in biological function of thyroid gland. Patients with subclinical hypothyroidism predominantly have increased thyroid volume whereas patients with more pronounced hypothyroidism have smaller thyroid volumes. Suggested mechanism for thyroid atrophy is thyrocyte death due to apoptosis. We performed the first genome-wide association study (GWAS) of thyroid volume in two groups of HT patients, depending on levothyroxine (LT4) therapy, and then meta-analysed across. Study included 345 HT patients in total and 6 007 322 common autosomal genetic variants. Underlying hypothesis was that genetic components that are involved in regulation of thyroid volume display their effect in specific pathophysiologic conditions of thyroid gland of HT patients. We additionally performed immunohistochemical analysis using thyroid tissues and analysed differences in expression levels of identified proteins and apoptotic marker between HT patients and controls. We found genome-wide significant association of two loci, both involved in apoptosis, with thyroid volume of HT patients: rs7212416 inside apoptosis-antagonizing transcription factor AATF (P = 8.95 × 10 −9) and rs10738556 near chromatin-remodeling SMARCA2 (P = 2.83 × 10 −8). In immunohistochemical analysis we observed that HT patients with homozygous AATF risk genotypes have decreased AATF expression (0.46-fold, P < 0.0001) and increased apoptosis (3.99-fold, P = 0.0001) in comparison to controls. HT patients with heterozygous SMARCA2 genotypes have decreased SMARCA2 expression, albeit without reaching statistical significance (1.07-fold, P = 0.5876), and significantly increased apoptosis (4.11-fold, p < 0.0001). By two lines of evidence we show that two highly plausible genetic loci, AATF and SMARCA2, may be involved in determining the thyroid volume of HT patients. The results of our study significantly add to the current knowledge of disturbed biological mechanisms in thyroid gland of HT patients.

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“…In addition, HIF-1 plays a critical role in immune escape and EMT of HCC [ 44 ]. Literature has shown that the interaction between thyroid hormone and its receptor plays an important role in the regulation of development and proliferation, and metastasis of HCC [ 45 ]. Research also showed that the occurrence of HBV-related HCC activates the Ras/MAPK signaling pathway which is correlated with a poor prognosis [ 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Systematically Exploring the Antitumor Mechanisms of Core Chinese Herbs on Hepatocellular Carcinoma: A Computational Study

Wang

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objective. Chinese herbs play a positive role in the management of hepatocellular carcinoma (HCC) in China. However, it is not clear which of Chinese herbs are critical for the treatment of HCC. Besides, mechanisms of CCHs in the treatment of HCC remain unclear. Hence, our goal is to identify the core Chinese herbs (CCHs) for treating HCC and explore their antitumor mechanism. Methods. Firstly, clinical traditional Chinese medicine (TCM) prescriptions for HCC were collected from Chinese National Knowledge Infrastructure (CNKI) database, and then, data mining software was used to identify CCHs. After that, bioactive compounds and corresponding target genes of CCHs were obtained using three TCM databases, and target genes of HCC were acquired from MalaCards and OMIM. Subsequently, common target genes of CCHs and HCC were screened. Moreover, biological functions and pathways were analyzed, and Cytoscape plugin cytoHubba was used to identify hub genes. Finally, prognostic values of hub genes were verified by survival analysis, and the molecular docking approach was utilized to validate the interactions between targets and bioactive compounds of CCHs. Results. Eight CCHs were determined from 630 prescriptions, and 100 bioactive compounds (e.g., quercetin and luteolin) and 126 common target genes were screened. Furthermore, common target genes of CCHs and HCC were mainly enriched in cancer-associated pathways, and six hub genes with statistical significance in survival analysis were selected as key target genes for molecular docking. Additionally, molecular docking showed that the bioactive compounds docked well with the protein receptors of key target genes. Conclusion. By combining data mining, network pharmacology, molecular docking, and survival analysis methods, we found that CCHs may play a therapeutic role in HCC through regulating the target genes and pathways related to cancer occurrence and development, angiogenesis, metastasis, and prognosis.

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Thyroid hormone in the regulation of hepatocellular carcinoma and its microenvironment

Cited by 23 publications

References 109 publications

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

Can network pharmacology identify the anti-virus and anti- inflammatory activities of Shuanghuanglian oral liquid used in Chinese medicine for respiratory tract infection?

AATF and SMARCA2 are associated with thyroid volume in Hashimoto’s thyroiditis patients

Systematically Exploring the Antitumor Mechanisms of Core Chinese Herbs on Hepatocellular Carcinoma: A Computational Study

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