The role of the novel LincRNA uc002jit.1 in NF-kB-mediated DNA damage repair in acute myeloid leukemia cells.

In this study, we identified a novel large intergenic noncoding RNA uc002jit.1 (D43770) from a lncRNA microarray. uc002jit.1 is 1800 nt long with a stable secondary structure. We first proved uc002jit.1 is a target gene of nuclear factor kappa B/RELA, RELA regulated uc002jit.1 transcription by binding to its promoter. Additionally, uc002jit.1 knockdown impaired the stability of poly (ADP-ribose) polymerase 1 (PARP1) mRNA, and then reduced PARP1 protein content and PARylation level upon DNA damage, thus inhibiting DNA damage repair in AML cells. Moreover, uc002jit.1 knockdown significantly inhibited AML cells proliferation and increased the sensitivity to chemotherapeutic drugs in vitro as well as in a mouse model in vivo. Overall, our study indicated that uc002jit.1 may be associated with the occurrence and prognosis of AML and could be a new diagnostic/prognostic biomarker and therapeutic target for AML. PMID: 32259522 [PubMed - as supplied by publisher]
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research

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;rôme Moreaux Cytogenetically normal acute myeloid leukemias (CN-AML) represent about 50% of total adult AML. Despite the well-known prognosis role of gene mutations such as NPM1 mutations of FLT3 internal tandem duplication (FLT3-ITD), clinical outcomes remain heterogeneous in this subset of AML. Given the role of genomic instability in leukemogenesis, expression analysis of DNA repair genes might be relevant to sharpen prognosis evaluation in CN-AML. A publicly available gene expression profile dataset from two independent cohorts of patients with CN-AML were analyzed (GSE12417). We investigated the prognostic ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
RAD52 aptamer regulates DNA damage repair and STAT3 in BRCA1/BRCA2‑deficient human acute myeloid leukemia. Oncol Rep. 2020 Aug 10;: Authors: Xu Y, Lin Y, Luo Y, Yang Y, Long B, Fang Z, Liu L, Zhang J, Zhang X Abstract RAD52 (Radiation sensitive 52) is a key factor in DNA damage repair (DDR) bypass, which participates in single‑strand annealing (SSA) after DNA damage end excision, while breast cancer type 1 susceptibility protein (BRCA1)/breast cancer type 2 susceptibility protein (BRCA2) play critical roles in homologous recombination (HR) repair. The present study aimed to determine whether RAD52...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Kevetrin induces apoptosis in TP53 wild‑type and mutant acute myeloid leukemia cells. Oncol Rep. 2020 Aug 11;: Authors: Napolitano R, De Matteis S, Carloni S, Bruno S, Abbati G, Capelli L, Ghetti M, Bochicchio MT, Liverani C, Mercatali L, Calistri D, Cuneo A, Menon K, Musuraca G, Martinelli G, Simonetti G Abstract Tumor protein p53 is a key regulator of several cellular pathways, including DNA repair, cell cycle and angiogenesis. Kevetrin exhibits p53‑dependent as well as‑independent activity in solid tumors, while its effects on leukemic cells remain unknown. The aim of the present study was to ...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
In this study, we investigated the relative potency of the nucleoside analogs and non-nucleoside analogs DHAs on DNA methylation reversal using DNA pyrosequencing. Additionally, we screened their effect on the enzymatic activity of the histone deacetylase sirtuin family (SIRT1, SIRT2, SIRT3, SIRT5 and SIRT6) using recombinant enzymes and nuclear lysates from leukemia cells. The nucleoside analogs were the most potent DHAs and increased the activity of SIRT6 without showing any significant increase in other isoforms. ChIP-Seq analysis of bone marrow cells derived from six acute myeloid leukemia (AML) patients and treated wi...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research
Maria Hernandez-Valladares Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Communication Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in acute myeloid leukemia cell lines and primary acute myeloid leukemia patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we found that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo ...
Source: Haematologica - Category: Hematology Authors: Tags: Haematologica Source Type: research
Pediatric myelodysplastic syndromes (MDS) represent a spectrum of rare hematopoietic stem cell disorders characterized by cytopenias, ineffective hematopoiesis, marrow dysplasia and risk for leukemic transformation. While some cases are likely acquired due to de novo transformation, germline mutations in DNA repair pathways, ribosomal pathways, the telomere complex or in hematopoietic transcription factors (e.g., CEBPA, RUNX1, GATA2 and ETV6) are predisposition syndromes underlying many pediatric cases of MDS and acute myeloid leukemia (AML).
Source: Biology of Blood and Marrow Transplantation - Category: Hematology Authors: Source Type: research
Abstract In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stim...
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
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