Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Paskeh, Mahshid Deldar Abad; Mirzaei, Sepideh; Ashrafizadeh, Milad; Zarrabi, Ali; Sethi, Gautam

doi:10.2147/jhc.s336858

Cited by 94 publications

(59 citation statements)

References 295 publications

(292 reference statements)

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“…Our study showed that the second most mutated in HCC patients is CTNNB1, and CTNNB1 gene mutation and overexpression contribute to hepatocellular carcinoma progression. In addition, β-catenin prevents apoptosis and enhances HCC cell migration by inducing EMT and upregulating MMP levels [44]. Clinical studies have con rmed the role of CTNNB1 mutations and βcatenin in HCC progression [45,46].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Pyroptosis-Related LncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Huang

Liu

Chen

et al. 2022

Preprint

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Background: Liver cancer is considered one of the prevalent malignancies, of which most are hepatocellular carcinoma (HCC). Pyroptosis is a form of inflammation that can mediate cellular programmed death. Long non-coding RNA (lncRNA) is one of the non-coding RNAs which performs powerful biological functions, and they exert an irreplaceable role in the regulation of many biological processes. However, pyroptosis-related lncRNAs expression and their correlation to the HCC patient prognosis remain to be investigated.Methods: Using The Cancer Genome Atlas (TCGA) database, we built a pyroptosis-related multi-lncRNA signature to predict the HCC patient prognosis. The least absolute shrinkage and selection operator (LASSO) Cox regression method was used to construct a pyroptosis-associated lncRNA signature to classify all HCC patients into high- and low-risk groups.Results: The low-risk group patients have a better prognosis. We identified the risk score as an independently predictor in HCC patients. Furthermore, chemotherapeutic drug sensitivity (gemcitabine, doxorubicin, mitomycin C and sorafenib), and immune cell expression (NK cells resting, Mast cells resting, M0 macrophages, Monocytes and CD8 T cells) showed significantly different infiltration degree between the two groups. We identified SC-5608, anisomycin and vancomycin as possible potential drug targets for the high-risk group patients. We performed enrichment analysis for the differential genes in the two groups of patients. Intriguingly, the result showed that targeting the wnt/β-catenin signal pathway could help to develop treatment strategies for patients with HCC. Conclusions: In conclusively, we found a signature of pyroptosis-related lncRNA for predicting independent HCC patient prognosis. The study provides new insights for reliably and accurately predicting prognosis and developing therapeutic strategies for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Identification of a Pyroptosis-Related LncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Huang

Liu

Chen

et al. 2022

Preprint

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“…Despite great advances in diagnostic methods, most HCC patients were still diagnosed in advanced stages, when therapies are mostly limited ( Huang et al, 2020 ). Moreover, anti-cancer agents often show less efficacy due to the difficulty of reaching the tumor site and exerting their anti-tumor activity ( Deldar Abad Paskeh et al, 2021 ). Since Wnt/β-catenin signaling can enhance proliferation and migration rates and drug resistance of HCC cells, thus, ENO3 may serve as a Wnt/β-catenin axis inhibitor and a specific therapeutic target for the treatment of HCC.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, many critical molecular alterations have been revealed during HCC, including TERT , TP53 , and CTNNB1 , etcetera ( Villanueva, 2019 ; Llovet et al, 2021 ). HCC cells have tremendous proliferation and metastasis capacities and are prone to drug resistance, which mediates their aggressive behavior ( Deldar Abad Paskeh et al, 2021 ). Despite significant progress in clinical management, the outcomes of HCC patients remain poor due to their rapid development and early recurrence ( Ge et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

ENO3 Inhibits Growth and Metastasis of Hepatocellular Carcinoma via Wnt/β-Catenin Signaling Pathway

Cui

Guo²,

Zhang³

et al. 2021

Front. Cell Dev. Biol.

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β-enolase (ENO3) is a metalloenzyme that functions during glycolysis and has been revealed ectopic expression in different cancers. However, the function and underlying modulatory mechanisms of ENO3 in hepatocellular carcinoma (HCC) are still elusive. Here, we discovered that ENO3 was remarkably down-regulated in human HCC tissue in contrast to those in noncancerous tissue. Moreover, low expression of ENO3 was related to the poor prognosis of HCC patients. Overexpression of ENO3 suppressed proliferative, migratory, and invasive abilities of HCC cells both in vitro and in vivo, whereas knocking down ENO3 led to the opposite effect. In addition, we revealed that ENO3 repressed the epithelial-mesenchymal transition (EMT) process with its biomarker variations. Mechanistic research unveiled that ENO3 suppressed the Wnt/β-catenin signal, which subsequently modulated the transcription of its target genes associated with the proliferation and metastasis capacity of HCC cells. Taken together, our study uncovered that ENO3 acted as a tumor inhibitor in HCC development and implied ENO3 as a promising candidate for HCC treatment.

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“…The role of NF‐κB signaling in gastrointestinal cancers has been investigated with greater details as compared to other cancer types (Manu et al, 2012; Mohan, Anilkumar et al, 2018). Liver cancer is among the common tumors of the gastrointestinal tract and it threatens the life of many people around the world (Deldar Abad Paskeh, Mirzaei et al, 2021; Mastron et al, 2015; Swamy et al, 2017). The activation of NF‐κB signaling promotes Snail expression to induce the EMT mechanism for enhancing metastasis and invasion of tumor cells.…”

Section: Nf‐κb and Emt Interaction In Various Cancersmentioning

confidence: 99%

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

Mirzaei

Saghari

Bassiri

et al. 2022

Journal Cellular Physiology

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118

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Metastasis of tumor cells is a complex challenge and significantly diminishes the overall survival and prognosis of cancer patients. The epithelial‐to‐mesenchymal transition (EMT) is a well‐known mechanism responsible for the invasiveness of tumor cells. A number of molecular pathways can regulate the EMT mechanism in cancer cells and nuclear factor‐kappaB (NF‐κB) is one of them. The nuclear translocation of NF‐κB p65 can induce the transcription of several genes involved in EMT induction. The present review describes NF‐κB and EMT interaction in cancer cells and their association in cancer progression. Due to the oncogenic role NF‐κB signaling, its activation enhances metastasis of tumor cells via EMT induction. This has been confirmed in various cancers including brain, breast, lung and gastric cancers, among others. The ZEB1/2, transforming growth factor‐β, and Slug as inducers of EMT undergo upregulation by NF‐κB to promote metastasis of tumor cells. After EMT induction driven by NF‐κB, a significant decrease occurs in E‐cadherin levels, while N‐cadherin and vimentin levels undergo an increase. The noncoding RNAs can potentially also function as upstream mediators and modulate NF‐κB/EMT axis in cancers. Moreover, NF‐κB/EMT axis is involved in mediating drug resistance in tumor cells. Thus, suppressing NF‐κB/EMT axis can also promote the sensitivity of cancer cells to chemotherapeutic agents.

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Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

Cited by 94 publications

References 295 publications

Identification of a Pyroptosis-Related LncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

Identification of a Pyroptosis-Related LncRNA Signature as a Novel Prognostic Biomarker for Hepatocellular Carcinoma

ENO3 Inhibits Growth and Metastasis of Hepatocellular Carcinoma via Wnt/β-Catenin Signaling Pathway

NF‐κB as a regulator of cancer metastasis and therapy response: A focus on epithelial–mesenchymal transition

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