Evaluation of the CRISPR/Cas9 directed mutant TP53 gene repair ıng effect in human prostate cancer cell line PC-3.

In this study, we aimed to evaluate the CRISPR/Cas9 repairing efficiency on TP53 414delC (p.K139fs*31) null mutation, located in the TP53 gene, of human prostate cancer cell line PC-3 in combination with ssODNs. According to the next-generation sequencing results, TP53 414delC mutation was repaired with an efficiency of 19.95% and 26.0% at the TP53 414delC position with ssODN1 and ssODN2 accompanied by sgRNA2 guided CRISPR/Cas9, respectively. Besides, qPCR and immunofluorescence analysis showed that PC-3 cells, the TP53 414delC mutation of which were repaired, expressed wild type p53 again. Also, significantly increased number of apoptotic cells, driven by the repaired TP53 gene were detected compared to the control cells by flow cytometry analysis. As a result, sgRNA2 guided CRISPR/Cas9 system accompanied by ssODN was shown to effectively repair the TP53 414delC gene region and inhibit the cell proliferation of PC-3 cells. Therefore, the effects of the TP53 414delC mutation repairment in PC-3 cells will be investigated in the in vivo models for tumor clearance analysis in the near future. PMID: 31571107 [PubMed - as supplied by publisher]
Source: Molecular Biology Reports - Category: Molecular Biology Authors: Tags: Mol Biol Rep Source Type: research

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AbstractPurpose of ReviewTo describe the epidemiology, pathogenesis, and management of vesicourethral anastomotic stenosis after prostate cancer treatment.Recent FindingsInjectable scar modulating agents administered at the time of direct visual internal urethrotomy of vesicourethral anastomotic stenoses have been shown to improve endoscopic treatment outcomes. Trials are ongoing to find the optimal agent and delivery system. Novel tissue engineering techniques are in development and hold promise.SummaryVesicourethral anastomotic stenosis after the treatment of prostate cancer is a challenging complication for patients and...
Source: Current Bladder Dysfunction Reports - Category: Urology & Nephrology Source Type: research
Authors: Schepisi G, Brighi N, Cursano MC, Gurioli G, Ravaglia G, Altavilla A, Burgio SL, Testoni S, Menna C, Farolfi A, Casadei C, Tonini G, Santini D, De Giorgi U Abstract Immunotherapy represents the new era of cancer treatment because of its promising results in various cancer types. In urological tumors, the use of the immune-checkpoint inhibitors (ICIs) is increasingly spreading. Although not all patients and not all diseases respond equally well to immunotherapy, there is an increasing need to find predictive markers of response to ICIs. Patient- and tumor-related factors may be involved in primary and secon...
Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
Authors: Morgans AK, Szymaniak BM Abstract The landscape of genetic testing for prostate cancer is rapidly evolving. There is increasing evidence that individuals with germline mutations in DNA-repair genes are more responsive to targeted therapies. Due to potential implications for treatment, these genes should be taken into consideration when determining the scope of genetic testing. PMID: 31629435 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Carroll PR, Witte JS, Parsons JK Abstract Men with germline mutations in DNA repair genes are at an increased risk of prostate cancer. These germline mutations are commonly seen in conjunction with somatic DNA repair gene mutations in prostate tumors. This indicates that men with a personal or family history of prostate cancer-as well as other cancer syndromes arising from mutations in DNA repair genes-should be considered for genetic testing and counseling. PMID: 31629425 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
This article summarizes a presentation at the 2019 Philadelphia Consensus Conference focused on the latest data at the intersection of germline and tumor genetic testing for prostate cancer patients. PMID: 31629422 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Knudsen KE Abstract Despite significant advances in understanding the biology of advanced prostate cancer and approval of novel therapeutic agents, there is no durable cure for metastatic disease. Recent findings unmasked the importance of androgen receptor (AR) signaling in regulation of DNA repair, and alterations of the AR-DNA repair factor axis were shown to promote aggressive phenotypes including metastasis. These and related findings underscore the importance of determining impact AR-DNA repair factor alterations on prostate cancer progression. PMID: 31629421 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Cheng HH Abstract Recent studies demonstrate that the prevalence of germline mutations in DNA repair genes in metastatic prostate cancer is higher than previously recognized, and is higher than in localized disease and in unaffected men. This is compelling evidence that specific gene dysfunction is critical in prostate cancer initiation and/or evolution to metastases. Applications to treatment in advanced disease are imminent, and further investigation in early-stage disease, as well as in diverse and at-risk populations will help maximize clinical benefit. PMID: 31629420 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
Authors: Boyle J, Cooney KA Abstract Germline pathogenic mutations in DNA repair genes have been linked to prostate cancer risk and aggressiveness. This observation was facilitated by tumor sequencing of men with advanced prostate cancer and has important implications for clinical management. In addition, cascade testing will identify at-risk individuals who should be assessed for cancer risk. PMID: 31629416 [PubMed - in process]
Source: Canadian Journal of Urology - Category: Urology & Nephrology Tags: Can J Urol Source Type: research
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Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
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