Description of CRISPR/Cas9 development and its prospect in hepatocellular carcinoma treatment

Wu, Xiaoling; Ma, Weijie; Mei, Chengjie; Chen, Xi; Yao, Ye; Liu, Yingyi; Qin, Xian; Yuan, Yufeng

doi:10.1186/s13046-020-01603-0

Cited by 15 publications

(14 citation statements)

References 100 publications

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“… 94 CRISPR-Cas9 has also shown great potential in the treatment of cancer, including HCC. 95 , 96 Wang et al reported that the knockout of CXC chemokine receptor 4 (CXCR4), associated with a poor prognosis in HCC, by CRISPR/Cas9 not only suppresses proliferation and invasion but also increases sensitivity to the anticancer drug cisplatin in HCC. 97 Another study has shown that the CRISPR/Cas9-mediated knockout of nuclear receptor binding SET domain-containing protein 1 inhibits the ability of HCC cells to proliferate and migrate.…”

Section: Overview Of Hcc Therapy Targeting Bmi1mentioning

confidence: 99%

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma

Wang

Fan

Sun

et al. 2022

Technol Cancer Res Treat

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Liver cancer has high rates of morbidity and mortality, and its treatment is a global health challenge. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancer cases. B-lymphoma Mo-MLV insertion region 1 ( BMI1) has been identified as a proto-oncogene, which contributes to the initiation and progression of many malignant tumors. BMI1 expression is upregulated in HCC, and it influences the occurrence and development of HCC by various mechanisms, such as the INK4a/ARF locus, NF-κB signaling pathway, and PTEN/PI3K/AKT signaling pathway. In addition, the expression of BMI1 is related to prognosis and recurrence of HCC. Hence, there is clear evidence that BMI1 is a novel and valid therapeutic target for HCC. Accordingly, the development of therapeutic strategies targeting BMI1 has been a focus of recent research, providing new directions for HCC treatment. This review summarizes the role of BMI1 in the occurrence and treatment of HCC, which will provide a basis for using BMI1 as a potential target for the development of therapeutic strategies for HCC.

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Section: Overview Of Hcc Therapy Targeting Bmi1mentioning

confidence: 99%

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma

Wang

Fan

Sun

et al. 2022

Technol Cancer Res Treat

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“…Cas9, a multifunctional protein, possesses two nuclease structural domains, HNH and RuvC. The HNH domain cuts the DNA strand complementarily paired with crRNA, and the RuvC domain cuts the other strand of double-stranded DNA (Stovicek et al 2017 ; Wu et al 2020 ). Cas9 becomes a single-stranded cleaved protein if one of the two structural domains is mutated, and if both are mutated, Cas9 becomes a protein with only DNA-binding activity (Young et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

CRISPR-cas9 screening identified lethal genes enriched in Hippo kinase pathway and of predictive significance in primary low-grade glioma

Mijiti,

Maimaiti,

Chen

et al. 2023

Mol Med

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Background Low-grade gliomas (LGG) are a type of brain tumor that can be lethal, and it is essential to identify genes that are correlated with patient prognosis. In this study, we aimed to use CRISPR-cas9 screening data to identify key signaling pathways and develop a genetic signature associated with high-risk, low-grade glioma patients. Methods The study used CRISPR-cas9 screening data to identify essential genes correlated with cell survival in LGG. We used RNA-seq data to identify differentially expressed genes (DEGs) related to cell viability. Moreover, we used the least absolute shrinkage and selection operator (LASSO) method to construct a genetic signature for predicting overall survival in patients. We performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the Weighted correlation network analysis (WGCNA). Finally, the study used western blot, qRT-PCR, and IHC to detect the expression of hub genes from signature in clinical samples. Results The study identified 145 overexpressed oncogenes in low-grade gliomas using the TCGA database. These genes were intersected with lethal genes identified in the CRISPR-cas9 screening data from Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct a genetic signature, and the Hippo signaling pathway was found to be the predominantly enriched pathway. The signature effectively distinguished between low- and high-risk patients, with high-risk patients showing a shorter overall survival duration. Differences in hub gene expression were found in different clinical samples, with the protein and mRNA expression of REP65 being significantly up-regulated in tumor cells. The study suggests that the Hippo signaling pathway may be a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including low-grade gliomas. Conclusion Our study identified a novel genetic signature associated with high-risk, LGG patients. We found that the Hippo signaling pathway was significantly enriched in this signature, indicating that it may be a critical regulator of tumor viability and proliferation in LGG. Targeting the Hippo pathway could be an innovative new strategy for treating LGG.

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“…Cas9, a multifunctional protein, possesses two nuclease structural domains, HNH and RuvC. The HNH domain cuts the DNA strand complementarily paired with crRNA, and the RuvC domain cuts the other strand of double-stranded DNA (Stovicek et al, 2017;Wu et al, 2020). Cas9 becomes a single-stranded cleaved protein if one of the two structural domains is mutated, and if both are mutated, Cas9 becomes a protein with only NDAbinding activity (Young et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

CRISPR-cas9 Screening Identified Lethal Genes Enriched in Hippo Kinase Pathway and of Prognosis Significance in primary Low-grade Glioma

Mijiti

Maimaiti

Chen

et al. 2022

Preprint

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Background Lethal genes in low-grade gliomas (LGGs) may have an essential prognostic significance and therefore need to be systematically analyzed. The purpose of this study is to analyze essential genes correlated with cell survival by evaluating CRISPR-cas9 screening data, leading to the identification of novel treatment targets for patients. Methods In this study, genes related to cell viability from the Depmap CRISPR-cas9 screen were intersected to differentially expressed genes (DEGs) between tumor and GTEx normal tissues from TCGA. The LASSO regression method was used to construct a signature that used to anticipate overall survival in patients with LGG. An evaluation of the signature was carried out using both multivariate and univariate Cox regression. Then, we determined which key pathways were modulated by this signature by comparing DEGs between low- and high-risk patients. WGCNA was conducted to identify modules associated with high-risk. In this study, we also performed enrichment analysis to identify pathways mediated by DEGs, overlapping genes, and genes shared in the WGCNA. Finally, we used to western blot, qRT-PCR and IHC to detect the expression of hub genes. Results Using the TCGA database, 145 oncogenes were identified as overexpressed. These genes were intersected with lethal genes identified in the Depmap database, which are enriched in Hippo pathways. A total of 19 genes were used to construct the gene signature by means of LASSO regression. The median risk score (0.752324) was employed to distinguish between low- and high-risk patients. The patients with high-risk characteristics showed a shorter OS duration in the internal training, the internal validation, and the external validation datasets. Ultimately, the Hippo signaling pathway was the predominantly enriched pathway in 145 genes, DEGs, and 3 modular genes in WGCNA. Finally, we found differences of hub genes expression in different clinical samples. Importantly, protein and mRNA expression of REP65 was significantly up-regulated in tumor cells both in the public cohort and our cohort. Conclusion The hippo signaling pathway detected based on CRISPR-cas9 screening is a critical regulator of viability and tumor proliferation and therefore is an innovative new target for treating cancerous brain tumors, including LGG.

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Description of CRISPR/Cas9 development and its prospect in hepatocellular carcinoma treatment

Cited by 15 publications

References 100 publications

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma

CRISPR-cas9 screening identified lethal genes enriched in Hippo kinase pathway and of predictive significance in primary low-grade glioma

CRISPR-cas9 Screening Identified Lethal Genes Enriched in Hippo Kinase Pathway and of Prognosis Significance in primary Low-grade Glioma

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