Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer

Waryah, Charlene Babra; Cursons, Joseph; Foroutan, Momeneh; Pflueger, Jahnvi; Wang, Edina; Molania, Ramyar; Sorolla, Anabel; Wallis, Christopher J.D.; Moses, Colette; Glas, Irina; Magalhães, Leandro; Thompson, Erik W.; Fearnley, Liam G.; Chaffer, Christine L.; Davis, Melissa J.; Papenfuss, Anthony T.; Redfern, Andrew; Lister, Ryan; Esteller, Manel; Blancafort, Pilar

doi:10.1002/advs.202301802

Cited by 11 publications

(4 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ROR1 is a type I transmembrane protein, that expresses during cancer and embryonic development and, has been identified as an oncofetal protein (Nicholas Borcherding, Pote and Gacche (2023) Frontiers in Molecular Biosciences frontiersin.org 2014). The aggressive behavior of various human cancers has been linked to the upregulation of ROR1.…”

Section: Crispr/cas9 and Receptor Tyrosine Kinase-like Orphan Recepto...mentioning

confidence: 99%

See 1 more Smart Citation

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics

Tiwari

Dubey

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

Clustered regularly interspaced short palindromic repeats (CRISPR) is a third-generation genome editing method that has revolutionized the world with its high throughput results. It has been used in the treatment of various biological diseases and infections. Various bacteria and other prokaryotes such as archaea also have CRISPR/Cas9 systems to guard themselves against bacteriophage. Reportedly, CRISPR/Cas9-based strategy may inhibit the growth and development of triple-negative breast cancer (TNBC) via targeting the potentially altered resistance genes, transcription, and epigenetic regulation. These therapeutic activities could help with the complex issues such as drug resistance which is observed even in TNBC. Currently, various methods have been utilized for the delivery of CRISPR/Cas9 into the targeted cell such as physical (microinjection, electroporation, and hydrodynamic mode), viral (adeno-associated virus and lentivirus), and non-viral (liposomes and lipid nano-particles). Although different models have been developed to investigate the molecular causes of TNBC, but the lack of sensitive and targeted delivery methods for in-vivo genome editing tools limits their clinical application. Therefore, based on the available evidences, this review comprehensively highlighted the advancement, challenges limitations, and prospects of CRISPR/Cas9 for the treatment of TNBC. We also underscored how integrating artificial intelligence and machine learning could improve CRISPR/Cas9 strategies in TNBC therapy.

show abstract

Section: Crispr/cas9 and Receptor Tyrosine Kinase-like Orphan Recepto...mentioning

confidence: 99%

“…In a recent study, Waryah et alemployed a TNBC model and achieved complete silencing of ZEB1 utilizing dCas9. Consequently, they observed a remarkably high specificity and near-total suppression of ZEB1 under in vivo condition ( Waryah et al, 2023 ).…”

Section: Dcas9mentioning

confidence: 99%

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics

Tiwari

Dubey

et al. 2023

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…CUT&RUN and base editing indicated that the NF-Y activator occupied the proximal CCAAT box, and the BCL11A initiated inhibition by binding competitively with NF-Y. Besides inhibiting gene expression, the dCas9-KRAB fusion protein can induce DNA methylation to explore the epigenome [46,47]. Thakore et al [29] targeted dCas9-KRAB to the HS2 enhancer that realizes specific induction of H3K9 trimethylation, which silenced the expression of multiple globin genes.…”

Section: Crispri Tools: Suppressing Gene Expression At the Transcript...mentioning

confidence: 99%

CRISPR/dCas9 Tools: Epigenetic Mechanism and Application in Gene Transcriptional Regulation

Cai,

Lv,

Shi

et al. 2023

IJMS

View full text Add to dashboard Cite

CRISPR/Cas9-mediated cleavage of DNA, which depends on the endonuclease activity of Cas9, has been widely used for gene editing due to its excellent programmability and specificity. However, the changes to the DNA sequence that are mediated by CRISPR/Cas9 affect the structures and stability of the genome, which may affect the accuracy of results. Mutations in the RuvC and HNH regions of the Cas9 protein lead to the inactivation of Cas9 into dCas9 with no endonuclease activity. Despite the loss of endonuclease activity, dCas9 can still bind the DNA strand using guide RNA. Recently, proteins with active/inhibitory effects have been linked to the end of the dCas9 protein to form fusion proteins with transcriptional active/inhibitory effects, named CRISPRa and CRISPRi, respectively. These CRISPR tools mediate the transcription activity of protein-coding and non-coding genes by regulating the chromosomal modification states of target gene promoters, enhancers, and other functional elements. Here, we highlight the epigenetic mechanisms and applications of the common CRISPR/dCas9 tools, by which we hope to provide a reference for future related gene regulation, gene function, high-throughput target gene screening, and disease treatment.

show abstract

“…The ZEBs are best known as key drivers of EMT by repressing CDH1 and the proepithelial miR-200 family members. Downstream targets of ZEB1 and ZEB2 have been well studied in the context of breast cancer and include key genes involved in epithelial plasticity and cellular polarity genes [88][89][90]. By targeting promoters of pro-epithelial genes, ZEBs are dominant regulators of EMT and tumor progression.…”

Section: Zeb1 and Zeb2mentioning

confidence: 99%

Unpacking the Complexity of Epithelial Plasticity: From Master Regulator Transcription Factors to Non-Coding RNAs

Waryah

Alves

Mazzieri

et al. 2023

Cancers

Self Cite

View full text Add to dashboard Cite

Cellular plasticity in cancer enables adaptation to selective pressures and stress imposed by the tumor microenvironment. This plasticity facilitates the remodeling of cancer cell phenotype and function (such as tumor stemness, metastasis, chemo/radio resistance), and the reprogramming of the surrounding tumor microenvironment to enable immune evasion. Epithelial plasticity is one form of cellular plasticity, which is intrinsically linked with epithelial–mesenchymal transition (EMT). Traditionally, EMT has been regarded as a binary state. Yet, increasing evidence suggests that EMT involves a spectrum of quasi-epithelial and quasi-mesenchymal phenotypes governed by complex interactions between cellular metabolism, transcriptome regulation, and epigenetic mechanisms. Herein, we review the complex cross-talk between the different layers of epithelial plasticity in cancer, encompassing the core layer of transcription factors, their interacting epigenetic modifiers and non-coding RNAs, and the manipulation of cancer immunogenicity in transitioning between epithelial and mesenchymal states. In examining these factors, we provide insights into promising therapeutic avenues and potential anti-cancer targets.

show abstract

Synthetic Epigenetic Reprogramming of Mesenchymal to Epithelial States Using the CRISPR/dCas9 Platform in Triple Negative Breast Cancer

Cited by 11 publications

References 113 publications

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics

CRISPR/Cas9 as a therapeutic tool for triple negative breast cancer: from bench to clinics

CRISPR/dCas9 Tools: Epigenetic Mechanism and Application in Gene Transcriptional Regulation

Unpacking the Complexity of Epithelial Plasticity: From Master Regulator Transcription Factors to Non-Coding RNAs

Contact Info

Product

Resources

About