TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells

Zhang, Kangjun; Fang, Taishi; Shao, Ya-jie

doi:10.2147/cmar.s297765

Cited by 15 publications

(13 citation statements)

References 39 publications

(48 reference statements)

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“…TGF-β promotes tumor migration and invasion through EMT (24,25). The effect of FXR1 on the TGF-β-induced migration and invasion in HCC cells was thus next assessed.…”

Section: F X R1 Promotes Slug/n-cadherin Expression a Nd Tgf-β-induce...mentioning

confidence: 99%

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo

et al. 2022

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Hepatocellular carcinoma (HCC) is a common malignancy that is associated with a poor prognosis. The extensively studied TGF-β pathway is mediated by SMAD proteins. FXR1, a protein-coding gene belonging to the fragile X-related (FXR) family, is involved in the TGF-β pathway. Previous studies have shown that FXR1 promotes the proliferation, invasion, and migration of colorectal cancer cells. The aim of the present study was to explore the effects of FXR1 on HCC via the TGF-β/SMAD signaling pathway. Immunohistochemical analysis was used to detect the expression of FXR1 in HCC and normal tissues. Western blotting was used to detect protein expression levels in the HCC cell lines, cell migration and invasion were assessed using Transwell assays, and cell proliferation was assessed using a colony formation assay. The ability of the liver cancer cells to grow in vivo was investigated using a nude mouse tumor-bearing model. The results showed that FXR1 expression was upregulated in HCC tissues compared with normal tissues. Knockdown of FXR1 resulted in reduced expression of SMAD2/3 and EMT-related proteins in HCC cells. In addition, FXR1 knockdown inhibited the proliferation, migration, and invasion of HCC cells. FXR1 knockdown also reversed the promoting effect of TGF-β on the invasive ability of HCC cells. Knockdown of SMAD2/3 reversed the increase in HCC cell invasion induced by FXR1 overexpression. Finally, upregulated FXR1 expression was associated with a poorer prognosis in patients with HCC. In conclusion, FXR1 promoted HCC proliferation, migration, and invasion through the regulation of SMAD2/3.

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“…TGF-β promotes tumor migration and invasion through EMT (24,25). The effect of FXR1 on the TGF-β-induced migration and invasion in HCC cells was thus next assessed.…”

Section: F X R1 Promotes Slug/n-cadherin Expression a Nd Tgf-β-induce...mentioning

confidence: 99%

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo

et al. 2022

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“…Upregulation of EZH2 expression in HCC is associated with unfavorable prognosis. The silence of EZH2 inhibits the HCC cell survival, migration and invasion, increased E-cadherin expression, and decreased N-cadherin and vimentin expression ( Zhang et al, 2021 ). Cell division cycle associated 8 (CDCA8) is an essential component of the chromosome passenger complex (CPC).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

Zeng²,

Ma³

et al. 2023

Front. Pharmacol.

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Background: Cuproptosis is a novel type of regulated cell death and is reported to promote tumor occurrence and progression. However, whether a cuproptosis-related signature has an impact on hepatocellular carcinoma (HCC) is still unclear.Materials and methods: We analyzed the transcriptome data of HCC from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, and searched for tumor types with different cuproptosis patterns through consistent clustering of cuproptosis genes. We then constructed a Cuproptosis-Related Genes (CRGs)-based risk signature through LASSO COX regression, and further analyzed its impact on the prognosis, clinical characteristics, immune cell infiltration, and drug sensitivity of HCC.Results: We identified the expression changes of 10 cuproptosis-related genes in HCC, and all the patients can be divided into two subtypes with different prognosis by applying the consensus clustering algorithm. We then constructed a cuproptosis-related risk signature and identified five CRGs, which were highly correlated with prognosis and representative of this gene set, namely G6PD, PRR11, KIF20A, EZH2, and CDCA8. Patients in the low CRGs signature group had a favorable prognosis. We further validated the CRGs signature in ICGC cohorts and got consistent results. Besides, we also discovered that the CRGs signature was significantly associated with a variety of clinical characteristics, different immune landscapes and drug sensitivity. Moreover, we explored that the high CRGs signature group was more sensitive to immunotherapy.Conclusion: Our integrative analysis demonstrated the potential molecular signature and clinical applications of CRGs in HCC. The model based on CRGs can precisely predict the survival outcomes of HCC, and help better guide risk stratification and treatment strategy for HCC patients.

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“…Research has also reported that decreased levels of CYP2C9 in HCC tissues [ 50 , 51 ], indicating the involvement of CYP2C9 in detoxification, may play an important role in the initiation of HCC. There is evidence that EZH2 is elevated in HCC and promotes proliferation, migration, and invasion of HCC cells, acted as a negative prognostic biomarker associated with immunosuppression, and is associated with sorafenib resistance in HCC [ 52 , 53 , 54 , 55 ]. SRXN1 , an antioxidant molecule, was significantly upregulated in HCC and its increasement might lessen BTG2 expression, resulting in an increase in HCC cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC

et al. 2023

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For hepatocellular carcinoma (HCC) patients, we attempted to establish a new oxidative stress (OS)-related prognostic model for predicting prognosis, exploring immune microenvironment, and predicting the immunotherapy response. Significantly differently expressed oxidative stress-related genes (DEOSGs) between normal and HCC samples from the Cancer Genome Atlas (TCGA) were screened, and then based on weighted gene coexpression network analysis (WGCNA), HCC-related hub genes were discovered. Based on the least absolute shrinkage and selection operator (LASSO) and cox regression analysis, a prognostic model was developed. We validated the prognostic model’s predictive power using an external validation cohort: the International Cancer Genome Consortium (ICGC).Then a nomogram was determined. Furthermore, we also examined the relationship of the risk model and clinical characteristics as well as immune microenvironment. 434 DEOSGs, comprising 62 downregulated and 372 upregulated genes (p < 0.05 and |log2FC| ≥ 1), and 257 HCC-related hub genes were recognized in HCC. Afterward, we built a five-DEOSG (LOX, CYP2C9, EIF2B4, EZH2, and SRXN1) prognostic risk model. Using the nomogram, the risk model was shown to have good prognostic value. Compared to the low risk group, HCC patients with high risk had poorer outcomes, worse pathological grades, and advanced tumor stages (p < 0.05). There were significant increases in LOX, EIF2B4, EZH2, and SRXN1 expression in HCC samples, while CYP2C9 expression was decreased. Finally, Real-time PCR (RT-qPCR) confirmed the mRNA expressions of five genes (CYP2C9, EIF2B4, EZH2, SRXN1, LOX) in HCC cell lines. Our study constructed a prognostic OS-related model with strong predictive power and potential as an immunosuppressive biomarker for HCC leading to improving prediction and providing new insights for HCC immunotherapy.

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TGF-β-MTA1-SMAD7-SMAD3-SOX4-EZH2 Signaling Axis Promotes Viability, Migration, Invasion and EMT of Hepatocellular Carcinoma Cells

Cited by 15 publications

References 39 publications

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo

FXR1 promotes proliferation, invasion and migration of hepatocellular carcinoma in vitro and in vivo

Identification and validation of a novel cuproptosis-related genes signature associated with prognosis, clinical implications and immunotherapy of hepatocellular carcinoma

Identification of Prognosis-Related Oxidative Stress Model with Immunosuppression in HCC

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