Emerging role of BAD and DAD1 as potential targets and biomarkers in cancer (Review)

Luo, Yulou; Wu, You; Huang, Hai; Yi, Na; Cao, Yan

doi:10.3892/ol.2021.13072

Cited by 10 publications

(7 citation statements)

References 97 publications

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“…BAD and BCL-2 remain with the BCL-2 gene, and their role is to promote apoptosis. The pro-apoptotic effect of the BAD gene is realized by the formation of heterodimers between the expression products of BAD gene and BCL-2 gene with the inhibition of the anti-apoptotic effect of BCL-2 ( 77 ). BAD gene plays a regulatory role in promoting apoptosis mainly through phosphorylation of Ser112, Ser136, and Ser155 ( 78 ).…”

Section: The Structural Domains Of Bcl-2 Family Proteinsmentioning

confidence: 99%

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

et al. 2022

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Apoptosis, as a very important biological process, is a response to developmental cues or cellular stress. Impaired apoptosis plays a central role in the development of cancer and also reduces the efficacy of traditional cytotoxic therapies. Members of the B-cell lymphoma 2 (BCL-2) protein family have pro- or anti-apoptotic activities and have been studied intensively over the past decade for their importance in regulating apoptosis, tumorigenesis, and cellular responses to anticancer therapy. Since the inflammatory response induced by apoptosis-induced cell death is very small, at present, the development of anticancer drugs targeting apoptosis has attracted more and more attention. Consequently, the focus of this review is to summarize the current research on the role of BCL-2 family proteins in regulating apoptosis and the development of drugs targeting BCL-2 anti-apoptotic proteins. Additionally, the mechanism of BCL-2 family proteins in regulating apoptosis was also explored. All the findings indicate the potential of BCL-2 family proteins in the therapy of cancer.

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Section: The Structural Domains Of Bcl-2 Family Proteinsmentioning

confidence: 99%

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

et al. 2022

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“…Previous studies have reported that the primary function of DAD1 is to negatively regulate programmed cell death and constitute the main component of oligosaccharyltransferase (OST) in the N-linked glycosylation of proteins 47 . The increased expression of DAD1 in hepatocellular carcinoma, colon cancer, small intestinal carcinoid, chronic lymphocytic leukemia, and prostate cancer indicates its great potential as a tumor treatment target of DAD1 41 . This work firstly verified the increased expression and anti-apoptotic function of DAD1 in BCa cells.…”

Section: Resultsmentioning

confidence: 99%

“…PLL was decorated with fluoroalkyl chains to form PLLF micelles, which self-assembled into non-compact NPs in aqueous solutions. Subsequently, the CRISPR-Cas9 plasmid targeting a glycosylation-associated gene DAD1, a new promising target for BCa therapy acquired through public data analyses and experimental verifications, was condensed by PLLF via electrostatic interactions to obtain stable NPs (denoted as PLLF/Cas9-sgDAD1) ( Figure 1 A ) 41 , 42 . With high cellular and mucosal penetrability, PLLF/Cas9-sgDAD1 NPs significantly downregulated the mRNA and protein levels of DAD1 in 5637 cells, resulting in cancer cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Targeting DAD1 gene with CRISPR-Cas9 system transmucosally delivered by fluorinated polylysine nanoparticles for bladder cancer intravesical gene therapy

Tang,

Yan,

et al. 2024

Theranostics

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Background: Intravesical chemotherapy is highly recommended after transurethral resection of bladder tumor for patients with bladder cancer (BCa). However, this localized adjuvant therapy has drawbacks of causing indiscriminate damage and inability to penetrate bladder mucosal. Methods: Fluorinated polylysine micelles (PLLF) were synthesized by reacting polylysine (PLL) with heptafluorobutyrate anhydride. Anti-apoptotic gene defender against cell death 1 (DAD1) was selected by different gene expression analysis between BCa patients and healthy individuals and identified by several biological function assays. The gene transfection ability of PLLF was verified by multiple in vitro and in vivo assays. The therapeutic efficiency of PLLF nanoparticles (NPs) targeting DAD1 were confirmed by intravesical administration using an orthotopic BCa mouse model. Results: Decorated with fluorinated chains, PLL can self-assemble to form NPs and condense plasmids with excellent gene transfection efficiency in vitro . Loading with the CRISPR-Cas9 system designed to target DAD1 (Cas9-sgDAD1), PLLF/Cas9-sgDAD1 NPs strongly inhibited the expression of DAD1 in BCa cells and induced BCa cell apoptosis through the MAPK signaling pathway. Furthermore, intravesical administration of PLLF/Cas9-sgDAD1 NPs resulted in significant therapeutic outcomes without systemic toxicity in vivo . Conclusion: The synthetized PLLF can transmucosally deliver the CRISPR-Cas9 system into orthotopic BCa tissues to improve intravesical instillation therapy for BCa. This work presents a new strategy for targeting DAD1 gene in the intravesical therapy for BCa with high potential for clinical applications.

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“…The rs8005354 is an intronic variant of the DAD1 gene. DAD1 has been identified as a regulator of apoptosis [ 21 ]. In animal model studies, deletion of DAD1 in the hamster TSBN7 cell line was shown to induce apoptosis [ 22 ], and the absence of DAD1 was associated with increased apoptosis in mice [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Selected Single-Nucleotide Variants in Patients with Neuroendocrine Tumors—Potential Clinical Relevance

Kurzyńska

Pach

Skalniak

et al. 2022

JCM

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Introduction: The genetic basis of neuroendocrine tumors (NETs), whose incidence is continuously increasing, is still not fully defined. The majority of NETs are sporadic, and only a small percentage occur as part of hereditary genetic syndromes. However, the associations of multiple genetic variants have been found as clinically relevant in several neoplasms. The aim of this study was to evaluate whether selected, literature-based genetic variants may have a potential role in NET susceptibility and clinical outcome in Polish patients. Materials/methods: A total of 185 patients recruited from one clinical center were enrolled. In the first part of the study, the molecular analysis including four single-nucleotide variants (rs8005354 (DAD1, NM_001344 intronic T/C substitution), rs2069762 (T/G substitution in the promoter region of the IL2 NM_000586), rs3731198 (CDKN2A, NM_000077 intronic A/G substitution), and rs1800872 (C/A substitution in the promoter region of the IL10 NM_000572)) was performed in 107 participants (49 patients with NETs with different primary site NETs and a control group of 58 healthy adult volunteers). In the second stage, the same single-nucleotide polymorphisms (SNPs) were assessed in 127 patients with NET and analyzed in terms of clinical data (primary site, serum CgA concentration, and metastatic disease). Results: The analysis of homozygotes revealed a statistically significant higher prevalence of TT homozygotes of variant rs3731198 in the control group (p = 0.0209). In NET patients, there was a statistically significant higher prevalence of GG homozygotes of variant rs1800872 (p = 0.003). There was a statistically significant correlation between the rs3731198 variant and lymph node metastases (p = 0.0038 with Bonferroni correction). Conclusions: Our study indicates that GG homozygotes of variant rs1800872 are more often observed in NET patients, while TT homozygotes of variant rs3731198 are less frequent in this group. The rs3731198 variant may be related to an increased risk of lymph node metastasis. Further, larger multicenter studies are warranted to evaluate the potential genetic factors of sporadic NETs.

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Emerging role of BAD and DAD1 as potential targets and biomarkers in cancer (Review)

Cited by 10 publications

References 97 publications

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

The role of BCL-2 family proteins in regulating apoptosis and cancer therapy

Targeting DAD1 gene with CRISPR-Cas9 system transmucosally delivered by fluorinated polylysine nanoparticles for bladder cancer intravesical gene therapy

Prevalence of Selected Single-Nucleotide Variants in Patients with Neuroendocrine Tumors—Potential Clinical Relevance

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