ASPM promotes hepatocellular carcinoma progression by activating Wnt/β‐catenin signaling through antagonizing autophagy‐mediated Dvl2 degradation

Zhang, Haifeng; Yang, Xin; Zhu, Lili; Li, Zhihui; Zuo, Peng; Wang, Peng; Feng, Jingyu; Mi, Yang; Zhang, Chengjuan; Xu, Yan; Jin, Ge; Zhang, Jianying; Ye, Hua

doi:10.1002/2211-5463.13278

Cited by 27 publications

(21 citation statements)

References 43 publications

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“…ASPM gene had abnormality due to its overexpression in HCC and played a vital role in cell proliferation and metastasis (Lin et al, 2008). It promotes the progression of HCC through the activation of Wnt/β‐catenin signaling (Zhang et al, 2021). This gene had missense mutations at 8 different locations in 2% of the patients on phosphorylation and ubiquitination post-transcriptional modification (PTM) sites (refer to table 4).…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis

Mishra

Singh

2022

Preprint

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Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if reached at metastatic phase. The novality of present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was done using RNA-Seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. Promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability leading to improper chromosome segregation causing aneuploidy. A 13-gene predictive model was obtained and validated using KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.

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Section: Discussionmentioning

confidence: 99%

Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis

Mishra

Singh

2022

Preprint

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“…Western blot assays were performed as described recently [ 27 ]. Briefly, cells were lysed on ice and proteins were fractionated by SDS-PAGE.…”

Section: Methodsmentioning

confidence: 99%

CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling

et al. 2022

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Objective Knowledge of the role of CYP2E1 in hepatocarcinogenesis is largely based on epidemiological and animal studies, with a primary focus on the role of CYP2E1 in metabolic activation of procarcinogens. Few studies have directly assessed the effects of CYP2E1 on HCC malignant phenotypes. Methods The expression of CYP2E1 in HCC tissues was determined by qRT-PCR, western blotting and immunohistochemistry. Overexpression of CYP2E1 in HCC cell was achieved by lentivirus transfection. The function of CYP2E1 were detected by CCK-8, wound healing, transwell assays, xenograft models and pulmonary metastasis model. TOP/FOPFlash reporter assay, western blotting, functional rescue experiments, Co-immunoprecipitation and reactive oxygen species detection were conducted to reveal the underlying mechanism of the tumor suppressive role of CYP2E1. Results CYP2E1 expression is down-regulated in HCC tissues, and this downregulation was associated with large tumor diameter, vascular invasion, poor differentiation, and shortened patient survival time. Ectopic expression of CYP2E1 inhibits the proliferation, invasion and migration and epithelial-to-mesenchymal transition of HCC cells in vitro, and inhibits tumor formation and lung metastasis in nude mice. Mechanistic investigations show that CYP2E1 overexpression significantly inhibited Wnt/β-catenin signaling activity and decreased Dvl2 expression in HCC cells. An increase in Dvl2 expression restored the malignant phenotype of HCC cells. Notably, CYP2E1 promoted the ubiquitin-mediated degradation of Dvl2 by strengthening the interaction between Dvl2 and the E3 ubiquitin ligase KLHL12 in CYP2E1-stable HCC cells. CYP2E1-induced ROS accumulation was a critical upstream event in the Wnt/β-Catenin pathway in CYP2E1-overexpressing HCC cells. Conclusions These results provide novel insight into the role of CYP2E1 in HCC and the tumor suppressor role of CYP2E1 can be attributed to its ability to manipulate Wnt/Dvl2/β-catenin pathway via inducing ROS accumulation, which provides a potential target for the prevention and treatment of HCC. Graphical Abstract

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“…The N6-methyladenosine modification of ASPM mRNA mediated by METTL3 promoted its expression in liver HCC [38]. ASPM also promotes tumor growth by antagonizing autophagymediated Dvl2 degradation and boosting Wnt/-catenin signaling [39].…”

Section: Validation Of Prognostic Value Of the Hub Genesmentioning

confidence: 96%

Screening and Identification of Key Genes in Hepatitis B Virus-Related Hepatocellular Carcinoma Through an Integrated Bioinformatics Approach

Nguyen

Tran

et al. 2022

Asian Pac J Cancer Biol

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Objective: Primary liver cancer is one of the main causes of cancer mortality globally, with hepatocellular carcinoma (HCC) being the most frequent type. Chronic hepatitis B virus (HBV) infection is leading cause of HCC. This study aimed to identify significant genes for predicting prognosis in HBV-associated HCC. Methods: The GSE121248 gene expression profile was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) for HBV-associated HCC were identified by analyzing this expression profile. Enrichment analyses were performed to discover the role of DEGs in biological processes, cell components, molecular functions, and pathways. Then, protein-protein interaction (PPI) was constructed and 5 hub genes were identified. Finally, survival analysis was conducted to validate the prognostic value of these genes. Results: A total of 20188 official gene symbols were found, and 119 DEGs were identified between HBV-associated HCC and normal liver tissues. The PPI network identified CCNB1, CDK1, TOP2A, RACGAP1, and ASPM as hub genes. Kaplan-Meier curves showed that the high expression of the hub genes had significantly lower survival. Conclusion: CCNB1, CDK1, TOP2A, RACGAP1, and ASPM could be potential prognostic biomarkers and therapeutic targets for HBV-associated HCC.

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ASPM promotes hepatocellular carcinoma progression by activating Wnt/β‐catenin signaling through antagonizing autophagy‐mediated Dvl2 degradation

Cited by 27 publications

References 43 publications

Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis

Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis

CYP2E1 plays a suppressive role in hepatocellular carcinoma by regulating Wnt/Dvl2/β-catenin signaling

Screening and Identification of Key Genes in Hepatitis B Virus-Related Hepatocellular Carcinoma Through an Integrated Bioinformatics Approach

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