BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair

Wang, Li-Po; Chen, Tzu‐Yu; Kang, Chun-Kai; Huang, Hsiang‐Po; Chen, Show‐Li

doi:10.1038/s41416-020-01086-y

Cited by 12 publications

(17 citation statements)

References 43 publications

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“…Reduced adult neurogenesis in hippocampus of BCAS2 cKO mice Previously, we found that BCAS2 regulated b-catenin [5,9]. The Wnt/b-catenin signaling pathway participates in hippocampal neurogenesis [14,15,22].…”

Section: Resultsmentioning

confidence: 91%

“…Association of BCAS2 and b-catenin in the hippocampus BCAS2 regulates b-catenin expression [5,9] and BCAS2 could regulate adult neurogenesis (Fig. 2 and 4), so we examined the association between BCAS2 and b-catenin in adult neurogenesis.…”

Section: Reduced Adult Neurogenesis In Hippocampus Of Mice With Bcas2 Knockdownmentioning

confidence: 99%

“…Previously, we found that BCAS2 regulates b-catenin [5,9]. SRY-box 2 (Sox2) and doublecortin (DCX) are widely used as markers for neurogenesis [21].…”

Section: Introductionmentioning

confidence: 99%

“…BCAS2 is involved in the Prp19-CDC5L spliceosome complex that regulates RNA splicing [8]. We found that BCAS2 upregulates β-catenin splicing [9], and BCAS2 conditional knockout (cKO) in the postnatal forebrain of animals caused microcephaly-like features, dendritic malformation, and poor learning and memory phenotypes due in part to downregulated β-catenin [5]. Disrupted Wnt/β-catenin signaling is involved in several neurodegenerative diseases such as Alzheimer disease and autism [10,11].…”

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confidence: 99%

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Breast Carcinoma-amplified Sequence 2 Regulates Adult Neurogenesis via β-catenin

Chen¹

2021

Preprint

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Background Breast carcinoma-amplified sequence 2 (BCAS2) regulates β-catenin gene splicing. The conditional knockout of BCAS2 expression in the forebrain (BCAS2 cKO) of mice confers impaired learning and memory along with decreased β-catenin expression. Because β-catenin reportedly regulates adult neurogenesis, we wondered whether BCAS2 could regulate adult neurogenesis via β-catenin. Methods BCAS2 regulating neurogenesis was investigated by characterizing BCAS2 cKO mice. Also, lentivirus-shBCAS2 was intracranially injected into the hippocampus of wild-type mice to knock down BCAS2 expression. We evaluated the rescue effects of BCAS2 cKO by intracranial injection of adeno-associated virus encoding BCAS2 (AAV-DJ8-BCAS2) and AAV-β-catenin gene therapy. Results To show that BCAS2-regulating adult neurogenesis via β-catenin, first, BCAS2 cKO mice showed low SRY-box 2–positive (Sox2+) neural stem cell proliferation and doublecortin-positive (DCX+) immature neurons. Second, stereotaxic intracranial injection of lentivirus-shBCAS2 knocked down BCAS2 in the hippocampus of wild-type mice, and we confirmed the BCAS2 regulation of adult neurogenesis via β-catenin. Third, AAV-DJ8-BCAS2 gene therapy in BCAS2 cKO mice reversed the low proliferation of Sox2+ neural stem cells and the decreased number of DCX+ immature neurons with increased β-catenin expression. Moreover, AAV-β-catenin gene therapy restored neuron stem cell proliferation and immature neuron differentiation, which further supports BCAS2 regulating adult neurogenesis via β-catenin. In addition, cells targeted by AAV-DJ8 injection into the hippocampus included Sox2 and DCX immature neurons, interneurons, and astrocytes. BCAS2 may regulate adult neurogenesis by targeting Sox2+ and DCX+ immature neurons for autocrine effects and interneurons or astrocytes for paracrine effects. Conclusions BCAS2 can regulate adult neurogenesis in mice via β-catenin.

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Section: Resultsmentioning

confidence: 91%

Section: Reduced Adult Neurogenesis In Hippocampus Of Mice With Bcas2 Knockdownmentioning

confidence: 99%

“…Previously, we found that BCAS2 regulates b-catenin [5,9]. SRY-box 2 (Sox2) and doublecortin (DCX) are widely used as markers for neurogenesis [21].…”

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Breast Carcinoma-amplified Sequence 2 Regulates Adult Neurogenesis via β-catenin

Chen¹

2021

Preprint

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“…69 Breast carcinoma-amplified sequence 2 ( BCAS2 ) takes part in DNA repair, cell cycle control, apoptosis and tissue homoeostasis. 70 On the other hand, GRB14 , ARG1 and BRE appeared as downregulated genes. A possible role of GRB14 for the proliferation of human breast and prostate cancers, 71 as well as functions of ARG1 in tumor immunity, tumor proliferation and metastasis, were previously reported.…”

Section: Resultsmentioning

confidence: 95%

Activity of Cordycepin From Cordyceps sinensis Against Drug-Resistant Tumor Cells as Determined by Gene Expression and Drug Sensitivity Profiling

Özenver

Boulos

Efferth

2021

Natural Product Communications

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Cordycepin is one of the substantial components of the parasitic fungus Cordyceps sinensis as well as other Cordyceps species. It exerts various effects such as antimetastatic, antiinflammatory, antioxidant, and neuroprotective activities. Assorted studies revealed in vitro and in vivo anticancer influence of cordycepin and put forward its potential for cancer therapy. However, the role of multidrug resistance-associated mechanisms for the antitumor effect of cordycepin has not been investigated in great detail thus far. Therefore, we searched cordycepin’s cytotoxicity with regard to well-known anticancer drug resistance mechanisms, including ABCB1, ABCB5, ABCC1, ABCG2, EGFR, and TP53, and identified putative molecular determinants related to the cellular responsiveness of cordycepin. Bioinformatic analyses of NCI microarray data and gene promoter transcription factor binding motif analyses were performed to specify the mechanisms of cordycepin towards cancer cells. COMPARE and hierarchical analyses led to the detection of the genes involved in cordycepin’s cytotoxicity and sensitivity and resistance of cell lines towards cordycepin. Tumor-type dependent response and cross-resistance profiles were further unravelled. We found transcription factors potentially involved in the common transcriptional regulation of the genes identified by COMPARE analyses. Cordycepin bypassed resistance mediated by the expression of ATP-binding cassete (ABC) transporters (P-gp, ABCB5, ABCC1 and BCRP) and mutant epidermal growth factor receptor (EGFR). The drug sensitivity profiles of several DNA Topo I and II inhibitors were significantly correlated with those of cordycepin’s activity. Among eight different tumor types, prostate cancer was the most sensitive, whereas renal carcinoma was the most resistant to cordycepin. NF-κB was discovered as a common transcription factor. The potential of cordycepin is set forth as a potential new drug lead by bioinformatic evaluations. Further experimental studies are warranted for better understanding of cordycepin’s activity against cancer.

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BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I

Sun,

Ye,

Cao

et al. 2024

Cell. Mol. Life Sci.

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Understanding the intricacies of homologous recombination during meiosis is crucial for reproductive biology. However, the role of alternative splicing (AS) in DNA double-strand breaks (DSBs) repair and synapsis remains elusive. In this study, we investigated the impact of conditional knockout (cKO) of the splicing factor gene Bcas2 in mouse germ cells, revealing impaired DSBs repair and synapsis, resulting in non-obstructive azoospermia (NOA). Employing crosslinking immunoprecipitation and sequencing (CLIP-seq), we globally mapped BCAS2 binding sites in the testis, uncovering its predominant association with 5’ splice sites (5’SS) of introns and a preference for GA-rich regions. Notably, BCAS2 exhibited direct binding and regulatory influence on Trp53bp 1 (codes for 53BP1) and Six6os1 through AS, unveiling novel insights into DSBs repair and synapsis during meiotic prophase I. Furthermore, the interaction between BCAS2, hnRNPH1, and SRSF3 was discovered to orchestrate Trp53bp1 expression via AS, underscoring its role in meiotic prophase I DSBs repair. In summary, our findings delineate the indispensable role of BCAS2-mediated post-transcriptional regulation in DSBs repair and synapsis during male meiosis. This study provides a comprehensive framework for unraveling the molecular mechanisms governing the post-transcriptional network in male meiosis, contributing to the broader understanding of reproductive biology. Supplementary Information The online version contains supplementary material available at 10.1007/s00018-024-05479-7.

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BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair

Cited by 12 publications

References 43 publications

Breast Carcinoma-amplified Sequence 2 Regulates Adult Neurogenesis via β-catenin

Breast Carcinoma-amplified Sequence 2 Regulates Adult Neurogenesis via β-catenin

Activity of Cordycepin From Cordyceps sinensis Against Drug-Resistant Tumor Cells as Determined by Gene Expression and Drug Sensitivity Profiling

BCAS2 and hnRNPH1 orchestrate alternative splicing for DNA double-strand break repair and synapsis in meiotic prophase I

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