Using a Dual CRISPR/Cas9 Approach to Gain Insight into the Role of LRP1B in Glioblastoma

Peixoto, Joana; Príncipe, Catarina; Pestana, Ana; Osório, Hugo; Pinto, M.; Prazeres, Hugo; Soares, Paula; Lima, Raquel T.

doi:10.3390/ijms241411285

Cited by 3 publications

(3 citation statements)

References 87 publications

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“…Cells were grown in sterilized round slides and transfected with siRNAs, as previously described, before being stained with "Flash Phalloidin™ Green 488" (Biolegend, San Diego, CA, USA) (1:200) and DAPI (1:1000) as previously described [49]. Samples were photographed using the fluorescence microscope Zeiss Axio Imager Z1 (Carl Zeiss, Oberkochen, Germany).…”

Section: Phalloidin Stainingmentioning

confidence: 99%

Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma

Teixeira,

Fernandes,

Bungărdean

et al. 2024

IJMS

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In a family with Familial Non-Medullary Thyroid Carcinoma (FNMTC), our investigation using Whole-Exome Sequencing (WES) uncovered a novel germline USP42 mutation [p.(Gly486Arg)]. USP42 is known for regulating p53, cell cycle arrest, and apoptosis, and for being reported as overexpressed in breast and gastric cancer patients. Recently, a USP13 missense mutation was described in FNMTC, suggesting a potential involvement in thyroid cancer. Aiming to explore the USP42 mutation as an underlying cause of FNMTC, our team validated the mutation in blood and tissue samples from the family. Using immunohistochemistry, the expression of USP42, Caspase-3, and p53 was assessed. The USP42 gene was silenced in human thyroid Nthy-Ori 3-1 cells using siRNAs. Subsequently, expression, viability, and morphological assays were conducted. p53, Cyclin D1, p21, and p27 proteins were evaluated by Western blot. USP42 protein was confirmed in all family members and was found to be overexpressed in tumor samples, along with an increased expression of p53 and cleaved Caspase-3. siRNA-mediated USP42 downregulation in Nthy-Ori 3-1 cells resulted in reduced cell viability, morphological changes, and modifications in cell cycle-related proteins. Our results suggest a pivotal role of USP42 mutation in thyroid cell biology, and this finding indicates that USP42 may serve as a new putative target in FNMTC.

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Section: Phalloidin Stainingmentioning

confidence: 99%

Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma

Teixeira,

Fernandes,

Bungărdean

et al. 2024

IJMS

Self Cite

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“…The use of lipid-based nano-delivery systems for in vivo CRISPR/Cas9 gene editing in brain cancer stem cells has also been explored, with promising results in disrupting the epidermal growth factor receptor variant III (EGFRvIII) mutation ( 46 ). Multiple studies have investigated the role of genes in GBM cell biology that can impact multiple survival pathways in cancers ( 47 , 48 ). Furthermore, CRISPR-Cas9 gene-edited CAR T cells demonstrated enhanced activity in preclinical glioma models ( 49 ).…”

Section: The Potential Of Crispr/cas9 In Cancer Treatmentmentioning

confidence: 99%

Revitalizing oral cancer research: Crispr-Cas9 technology the promise of genetic editing

S. V.,

Augustine,

Mushtaq

et al. 2024

Front. Oncol.

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This review presents an in-depth analysis of the immense potential of CRISPR-Cas9 technology in revolutionizing oral cancer research. It underscores the inherent limitations of conventional treatments while emphasizing the pressing need for groundbreaking approaches. The unparalleled capability of CRISPR-Cas9 to precisely target and modify specific genes involved in cancer progression heralds a new era in therapeutic intervention. Employing genome-wide CRISPR screens, vulnerabilities in oral cancer cells can be identified, thereby unravelling promising targets for therapeutic interventions. In the realm of oral cancer, the disruptive power of CRISPR-Cas9 manifests through its capacity to perturb genes that are intricately associated with drug resistance, consequently augmenting the efficacy of chemotherapy. To address the challenges that arise, this review diligently examines pertinent issues such as off-target effects, efficient delivery mechanisms, and the ethical considerations surrounding germline editing. Through precise gene editing, facilitated by CRISPR/Cas9, it becomes possible to overcome drug resistance by rectifying mutations, thereby enhancing the efficacy of personalized treatment strategies. This review delves into the prospects of CRISPR-Cas9, illuminating its potential applications in the domains of medicine, agriculture, and biotechnology. It is paramount to emphasize the necessity of ongoing research endeavors and the imperative to develop targeted therapies tailored specifically for oral cancer. By embracing this comprehensive overview, we can pave the way for ground-breaking treatments that instill renewed hope for enhanced outcomes in individuals afflicted by oral cancer.

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“…As previously mentioned, the presence of genetic mutations, including chromosomal changes such as the loss of chromosomes 10 and 9p, and the gain of chromosomes 7 and 19, suggests the potential utility of gene-oriented therapy as an option in the treatment of GBM [8,9]. One such approach that has garnered significant interest in the last decade across various medical conditions is the Clustered Regularly Interspaced Short Palindromic Repeat CRISPR-associated (Cas) nuclease 9 (CRISPR-Cas9) system [10], which facilitates gene editing technology [11]. CRISPR is recognized as the fastest, cheapest, most versatile, and most reliable gene editing tool available, extensively employed for uncovering genetic alterations, oncogenic targets, and epigenetic regulation.…”

Section: Introductionmentioning

confidence: 99%

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review

Begagić,

Bečulić,

Đuzić

et al. 2024

Biomedicines

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This scoping review examines the use of CRISPR/Cas9 gene editing in glioblastoma (GBM), a predominant and aggressive brain tumor. Categorizing gene targets into distinct groups, this review explores their roles in cell cycle regulation, microenvironmental dynamics, interphase processes, and therapy resistance reduction. The complexity of CRISPR-Cas9 applications in GBM research is highlighted, providing unique insights into apoptosis, cell proliferation, and immune responses within the tumor microenvironment. The studies challenge conventional perspectives on specific genes, emphasizing the potential therapeutic implications of manipulating key molecular players in cell cycle dynamics. Exploring CRISPR/Cas9 gene therapy in GBMs yields significant insights into the regulation of cellular processes, spanning cell interphase, renewal, and migration. Researchers, by precisely targeting specific genes, uncover the molecular orchestration governing cell proliferation, growth, and differentiation during critical phases of the cell cycle. The findings underscore the potential of CRISPR/Cas9 technology in unraveling the complex dynamics of the GBM microenvironment, offering promising avenues for targeted therapies to curb GBM growth. This review also outlines studies addressing therapy resistance in GBM, employing CRISPR/Cas9 to target genes associated with chemotherapy resistance, showcasing its transformative potential in effective GBM treatments.

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Using a Dual CRISPR/Cas9 Approach to Gain Insight into the Role of LRP1B in Glioblastoma

Cited by 3 publications

References 87 publications

Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma

Investigating USP42 Mutation as Underlying Cause of Familial Non-Medullary Thyroid Carcinoma

Revitalizing oral cancer research: Crispr-Cas9 technology the promise of genetic editing

CRISPR/Cas9-Mediated Gene Therapy for Glioblastoma: A Scoping Review

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