The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

Jia, Wentao; Liang, Shufang; Cheng, Baohua; Ling, Changquan

doi:10.3389/fonc.2021.763519

Cited by 22 publications

(16 citation statements)

References 162 publications

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“…Traditional Chinese medicine exhibits various unique properties like varied active substances, multiple key targets, and low toxicity [39]. More importantly, it has superior antitumor properties and can be used to treat different tumors, such as esophageal cancer, liver cancer, pancreatic cancer, and breast cancer [40][41][42][43]. The present study identified the key active ingredients and possible detailed molecular mechanisms of Dahuang against hepatoma through network pharmacology, molecular docking, and survival analysis.…”

Section: Discussionmentioning

confidence: 93%

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

Wang

et al. 2022

BioMed Research International

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Hepatoma is one of the most common malignant tumors. The incidence rate is high in developing countries, and China has the most significant number of cases. Dahuang is a classic traditional antitumor drug commonly used in China and has also been applied to treat hepatoma. However, the potential mechanism of Dahuang in treating hepatoma is not clear. Therefore, this study is aimed at elucidating the possible molecular mechanism and key targets of Dahuang using methods of network pharmacology, molecular docking, and survival analysis. Firstly, the active ingredients and key targets of Dahuang were analyzed through public databases, and then the drug-ingredient-target-disease network diagram of Dahuang against hepatoma was constructed. Five main active components and five core targets were determined according to the enrichment degree. Enrichment analysis demonstrated that Dahuang treated hepatoma through the multiple pathways in cancer. Additionally, molecular docking predicted that aloe-emodin and PIK3CG depicted the best binding energy. Survival analysis indicated that a high/ESR1 gene expression had a relatively good prognosis for patients with hepatoma ( p < 0.05 ). In conclusion, the current study results demonstrated that Dahuang could treat hepatoma through a variety of active ingredients, targets, and multiantitumor pathways. Moreover, it effectively improved the prognosis of hepatoma patients. ESR1 is the potential key gene that is beneficial for the survival of hepatoma patients. Also, aloe-emodin and beta-sitosterol are the two main active crucial ingredients for hepatoma treatment. The study also provided some functional bases and references for the development of new drugs, target mining, and experimental animal research of hepatoma in the future.

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Section: Discussionmentioning

confidence: 93%

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

Wang

et al. 2022

BioMed Research International

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“…Apart from the infiltrating immune cells, as the main component of tumor stroma, CAFs participated in the formation of TIME and were involved in the tumor progression and prognosis in HCC (Jia et al, 2021). RAB42 expression was found to be significantly correlated with CAFs in HCC.…”

Section: Discussionmentioning

confidence: 94%

“…Cancer-associated fibroblasts (CAFs) constitute the majority components of stroma in tumor and play multiple roles in facilitating tumor cells proliferation, migration, stemness and supporting the formation of TIME in HCC (Jia et al, 2021). We, therefore, investigated the possible association between the infiltration level of CAFs and the RAB42 expression in HCC.…”

Section: Correlation Between Rab42 Expression and Cancer-associated F...mentioning

confidence: 99%

RAB42 is a Potential Biomarker that Correlates With Immune Infiltration in Hepatocellular Carcinoma

Peng

Du²,

Zhang³

2022

Front. Mol. Biosci.

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Backgrounds: Hepatocellular carcinoma (HCC) is a malignant cancer with high mortality. Previous studies have reported that RAB42 is associated with prognosis and progression in glioma. However, the role of RAB42 in HCC is still unknown. Therefore, we aimed to elucidate the value of RAB42 in the predicting prognosis of HCC, and its relationship with immune cells infiltration.Methods: UALCAN, HCCDB, and MethSurv databases were used to examine the expression and methylation levels of RAB42 in HCC and normal samples. cBioPortal and MethSurv were used to identify genetic alterations and DNA methylation of RAB42, and their effect on prognosis. The correlations between RAB42 and the immune cells and cancer-associated fibroblasts infiltration were analyzed by TIMER, TISIDB, and GEPIA database. The LinkedOmics database was used to analyze the enriched pathways associated with genes co-expressed with RAB42. EdU assay was used to evaluate the proliferation ability of liver cancer cells, and transwell assay was used to detect the invasion and migration ability of liver cancer cells.Results: The expression levels of RAB42 were increased in HCC tissues than that in normal tissues. Highly expressed RAB42 was significantly correlated with several clinical parameters of HCC patients. Moreover, increased RAB42 expression clearly predicted poor prognosis in HCC. Furthermore, multivariate Cox regression analysis showed that RAB42 was an independent prognostic factor in HCC. The RAB42 genetic alteration rate was 5%. RAB42 DNA methylation in HCC tissues was lower than that in normal tissues. Among the 7 DNA methylation CpG sites, two were related to the prognosis of HCC. The results of gene set enrichment analysis (GSEA) showed that RAB42 was associated with various immune cells and cancer-associated fibroblasts infiltration in HCC. Meanwhile, we found RAB42 methylation was strongly correlated with immune infiltration levels, immunomodulators, and chemokines. Experiments in vitro indicated that knockdown of RAB42 inhibited the proliferation, invasion, and migration of liver cancer cells.Conclusions: Our study highlights the clinical importance of RAB42 in HCC and explores the effect of RAB42 on immune infiltration in the tumor microenvironment, and RAB42 may act as a pro-oncogene that promotes HCC progression.

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“…TCM has been proved to reduce the toxicity of chemotherapy drugs, enhance the sensitivity of radiotherapy, minimize the side effects of radiotherapy, and improve the immunity of patients in the treatment of lung cancer [ 22 ]. Moreover, it may also have a potential role in anti-recurrence and metastasis [ 23 ]. TCM against lung cancer can stabilize lesion conditions, prolong the survival period of patients, and benefit patients with better quality of life.…”

Section: Discussionmentioning

confidence: 99%

Arisaema heterophyllum Blume Monomer Stigmasterol Targets PPARγ and Inhibits the Viability and Tumorigenicity of Lung Adenocarcinoma Cells NCI-H1975

Song

Wang

Lai

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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To clarify the regulatory effect and molecular mechanism of Arisaema heterophyllum Blume (AhBl) monomer stigmasterol on lung adenocarcinoma in human lung adenocarcinoma cells NCI-H1975 cultured in vitro and in nude mice. Oil red O staining, free fatty acid detection, adenosine triphosphate (ATP), and NADPH were applied to elucidate the regulatory effect of stigmasterol on the energy metabolism of NCI-H1975 cells. Simultaneously, colony formation assay and nude mouse tumorigenesis were performed to clarify the underlying mechanisms of stigmasterol on the proliferation and tumorigenesis of NCI-H1975 cells. Furthermore, peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor GW9662 was supplemented to determine the expression changes of cyclins to clarify the regulation mechanism of stigmasterol. The results revealed that stigmasterol administration markedly inhibited the viability but promoted lipid deposition of NCI-H1975 cells. Meanwhile, the reduction of cell energy metabolism affected cell proliferation and colony formation. qPCR and western blot assays indicated that stigmasterol played a role in regulating the expression of cyclins and PPARγ signaling pathway proteins. Nude mouse tumorigenesis suggested that tumor size and weight in the stigmasterol-treated group were apparently lower as compared with the control group. Tumor tissue cells developed varying degrees of degeneration and large areas of ischemic necrosis presented in the central and peripheral cells. Immunohistochemistry results revealed that Ki67 expression in the stigmasterol group was substantially inhibited, while PPARγ expression was greatly elevated as compared with the control. GW9662 could mediate the inhibitory effect of stigmasterol on NCI-H1975 cells. The current study demonstrated that stigmasterol targeted PPARγ and inhibited the viability and tumorigenicity of lung adenocarcinoma cells NCI-H1975.

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The Role of Cancer-Associated Fibroblasts in Hepatocellular Carcinoma and the Value of Traditional Chinese Medicine Treatment

Cited by 22 publications

References 162 publications

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

Investigating the Role of Dahuang in Hepatoma Treatment Using Network Pharmacology, Molecular Docking, and Survival Analysis

RAB42 is a Potential Biomarker that Correlates With Immune Infiltration in Hepatocellular Carcinoma

Arisaema heterophyllum Blume Monomer Stigmasterol Targets PPARγ and Inhibits the Viability and Tumorigenicity of Lung Adenocarcinoma Cells NCI-H1975

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