CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway

Chen, Jiang; Shi, Jianhua; Shao, Huijiang; Li, Bixia; Ji, Tong; Staiculescu, Daniel; He, Junyu; Zhao, Jie; Cai, Ling; Liang, Xiao; Xu, Junjie; Cai, Xiujun

doi:10.1007/s11427-021-2067-7

Cited by 10 publications

(6 citation statements)

References 62 publications

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“…A positive feedback loop resulted from FGF21 binding to NRF2 through its C-terminus, which reduced NRF2’s ubiquitination and stabilized the protein. In light of these findings, inhibiting FGF21 may be useful for managing sorafenib resistance in HCC [ 118 ].…”

Section: Methodsmentioning

confidence: 99%

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

AMJAD,

PEZZANI,

SOKOUTI

2024

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Noncoding RNAs instruct the Cas9 nuclease to site-specifically cleave DNA in the CRISPR/Cas9 system. Despite the high incidence of hepatocellular carcinoma (HCC), the patient’s outcome is poor. As a result of the emergence of therapeutic resistance in HCC patients, clinicians have faced difficulties in treating such tumor. In addition, CRISPR/Cas9 screens were used to identify genes that improve the clinical response of HCC patients. It is the objective of this article to summarize the current understanding of the use of the CRISPR/Cas9 system for the treatment of cancer, with a particular emphasis on HCC as part of the current state of knowledge. Thus, in order to locate recent developments in oncology research, we examined both the Scopus database and the PubMed database. The ability to selectively interfere with gene expression in combinatorial CRISPR/Cas9 screening can lead to the discovery of new effective HCC treatment regimens by combining clinically approved drugs. Drug resistance can be overcome with the help of the CRISPR/Cas9 system. HCC signature genes and resistance to treatment have been uncovered by genome-scale CRISPR activation screening, although this method is not without limitations. It has been extensively examined whether CRISPR can be used as a tool for disease research and gene therapy. CRISPR and its applications to tumor research, particularly in HCC, are examined in this study through a review of the literature.

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Section: Methodsmentioning

confidence: 99%

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

AMJAD,

PEZZANI,

SOKOUTI

2024

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“…Moreover, FGF21 showed a positive feedback loop with NRF2 accounting for sorafenib's resistance. Higher FGF21 expression was correlated with more resistance to sorafenib treatment in HCC patients, and intra-tumoral FGF21 knockdown effectively inhibited tumor growth in sorafenib-resistant HCC animal models 94 . These findings indicated that the pathological upregulation of FGF21 promoted tumor development.…”

Section: Fgf21 Is a Promising Biomarker With Pleiotropic Activities I...mentioning

confidence: 95%

Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers

Sui

Chen

2022

Int. J. Biol. Sci.

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Fibroblast growth factor (FGF) 21 is one of the FGF members with special endocrine properties. In the last twenty years, it has attracted intense research and development for its physiological functions that respond to dietary manipulation, pharmacological benefits of improving the macronutrient metabolism, and clinical values as a biomarker of various human diseases. Generally, FGF21 can be produced by major metabolic organs, but only the subgroup from the liver shows canonical endocrine properties, which emphasizes the special value of delineating the unique secretory and functional characteristics of hepatic FGF21. There has been a growth in literature to address the extra-hepatic activities of FGF21, and many striking findings have therefore been published. Yet, they are fragmented and scattered, and controversies are raised from divergent findings. For this reason, there is a need for a systematic and critical evaluation of current research in this aspect. In this review, we focus on the current knowledge about the molecular biology of endocrine FGF21, especially present details on the regulation of circulating levels of FGF21. We also emphasize its emerging roles in inter-organ crosstalk and cancer development.

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“…Nuclear factor erythroid 2-related factor 2 (NRF2) is an upstream transcription factor of FGF21 which plays an important role in regulating cellular oxidative stress response and protecting against toxic and oxidative stress. 65 , 66 Using CRISPR/CAS9 genome library screening, it is found that by binding to NRF2, FGF21 stabilizes NRF2 and reduces its ubiquitination, generating a positive feedback loop in sorafenib-resistant HCC. 66 In db/db mice, both plasma FGF21 level and hepatic FGF21 expression were observed to be up-regulated in the administration of CDDO-Im (a potent Nrf2 inducer).…”

Section: The Interplay Between Autophagy and Liver Diseasesmentioning

confidence: 99%

“… 65 , 66 Using CRISPR/CAS9 genome library screening, it is found that by binding to NRF2, FGF21 stabilizes NRF2 and reduces its ubiquitination, generating a positive feedback loop in sorafenib-resistant HCC. 66 In db/db mice, both plasma FGF21 level and hepatic FGF21 expression were observed to be up-regulated in the administration of CDDO-Im (a potent Nrf2 inducer). The up-regulation of FGF21 was reversed in Nrf2 knockout db/db mice.…”

Section: The Interplay Between Autophagy and Liver Diseasesmentioning

confidence: 99%

FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases

Shen,

Yang,

Chen

et al. 2024

Genes & Diseases

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CRISPR-Cas9-based genome-wide screening identified novel targets for treating sorafenib-resistant hepatocellular carcinoma: a cross-talk between FGF21 and the NRF2 pathway

Cited by 10 publications

References 62 publications

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

A review of the literature on the use of CRISPR/Cas9 gene therapy to treat hepatocellular carcinoma

Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers

FGF21-mediated autophagy: Remodeling the homeostasis in response to stress in liver diseases

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