European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 263, С. 115952 - 115952
Опубликована: Ноя. 16, 2023
Язык: Английский
BMC Cancer, Год журнала: 2025, Номер 25(1)
Опубликована: Апрель 10, 2025
Язык: Английский
Процитировано
0
Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)
Опубликована: Апрель 17, 2025
Abstract Background The plasma cell malignancy multiple myeloma (MM) remains incurable due to the inevitable development of drug resistance (DR). Epigenetic modifiers are frequently mutated or deregulated in MM patients, contributing progression and relapse. Overexpression de novo DNA methyltransferase 3B (DNMT3B) has been reported, correlating with poor prognosis. However, its exact role biology relapse elusive. Methods To evaluate basal expression prognostic value DNMT3B mRNA terms overall survival publicly available gene profiling datasets GSE2658, GSE9782, GSE4581, E-MTAB-372, E-TABM-1088 E-TABM-937 were used. Both selective inhibitor Nanaomycin A genetic knockdown using a doxycycline inducible shRNA against used target DNMT3B. Viability apoptosis assessed respectively CellTiter-Glo assay AnnexinV/7AAD stainings. Cell proliferation was measured by BrdU incorporation cycle analysis, while clonogenic capacity evaluated colony formation assay. Finally, RNA-seq performed upon knockdown. Results Here, we show that is significantly increased relapsed setting high levels strongly disease high-risk disease, irrespective treatment. Targeting either inhibition impaired growth, clonogenicity. Moreover, reduced viability primary cells from newly diagnosed patients. Mechanistic studies revealed mainly affects stemness-related transcriptional programs. Notably, depletion affected stability master regulator MYC, thereby reducing c-MYC both parental overexpressing cells. (re)sensitized bortezomib, melphalan anti-CD38 monoclonal antibodies (daratumumab, isatuximab). Conclusion Collectively, our findings uncover as targetable vulnerability patients DNMT3B/MYC levels.
Язык: Английский
Процитировано
0
International Ophthalmology, Год журнала: 2024, Номер 44(1)
Опубликована: Фев. 16, 2024
Язык: Английский
Процитировано
3
Clinical and Experimental Medicine, Год журнала: 2024, Номер 24(1)
Опубликована: Май 2, 2024
Abstract Long non-coding RNAs (lncRNAs) are transcripts that contain more than 200 nucleotides. Despite their inability to code proteins, multiple studies have identified important role in human cancer through different mechanisms. LncRNA lysyl oxidase like 1 antisense RNA (LOXL1-AS1), a newly discovered lncRNA located on chromosome 15q24.1, has recently been shown be involved the occurrence and progression of various malignancies, such as colorectal cancer, gastric hepatocellular carcinoma, prostate non-small cell lung ovarian cervical breast glioma, thymic pancreatic carcinoma. LOXL1-AS1 acts competitive endogenous (ceRNA) via sponging miRNAs, including miR-374b-5p, miR-21, miR-423-5p, miR-589-5p, miR-28-5p, miR-324-3p, miR-708-5p, miR-143-3p, miR-18b-5p, miR-761, miR-525-5p, miR-541-3p, miR-let-7a-5p, miR-3128, miR-3614-5p, miR-377-3p miR-1224-5p promote tumor proliferation, invasion, migration, apoptosis, cycle, epithelial–mesenchymal transformation (EMT). In addition, is regulation P13K/AKT MAPK signaling pathways. This article reviews current understanding biological function clinical significance cancers. These findings suggest may both reliable biomarker potential therapeutic target for
Язык: Английский
Процитировано
3
Clinical and Experimental Pharmacology and Physiology, Год журнала: 2024, Номер 51(7)
Опубликована: Май 14, 2024
Cervical cancer (CC) is a gynaecological malignancy tumour that seriously threatens women's health. Recent evidence has identified interferon regulatory factor 5 (IRF5), nucleoplasm shuttling protein, pivotal transcription regulating the growth and metastasis of various human tumours. This study aimed to investigate function molecular basis IRF5 in CC development. IRF5, protein phosphatase 6 catalytic subunit (PPP6C) methyltransferase-like 3 (METTL3) mRNA levels were evaluated by quantitative real-time (qRT)-polymerase chain reaction (PCR). PPP6C, METTL3, B-cell lymphoma 2 Bax detected using western blot. Cell proliferation, migration, invasion, angiogenesis apoptosis determined colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, tube formation assay flow cytometry assay, respectively. Glucose uptake lactate production measured commercial kits. Xenograft vivo was used explore role IRF5. After JASPAR predication, binding between PPP6C promoter verified chromatin immunoprecipitation dual-luciferase reporter assays. Moreover, interaction METTL3 methylated RNA (MeRIP). highly expressed tissues cells. silencing significantly inhibited cell glycolytic metabolism cells, while induced apoptosis. Furthermore, absence hindered vivo. At level, might bind with positively regulate expression mRNA. Meanwhile, as downstream target METTL3-mediated m6A modification. modification promote malignant progression which provide promising therapeutic for treatment.
Язык: Английский
Процитировано
3
Biochemical Pharmacology, Год журнала: 2024, Номер 226, С. 116406 - 116406
Опубликована: Июль 4, 2024
Язык: Английский
Процитировано
3
Molecular Medicine Reports, Год журнала: 2024, Номер 30(3)
Опубликована: Июль 8, 2024
Cordycepin is a nucleoside molecule found in
Язык: Английский
Процитировано
3
Toxicology, Год журнала: 2023, Номер 500, С. 153660 - 153660
Опубликована: Ноя. 2, 2023
Язык: Английский
Процитировано
7
Marine Pollution Bulletin, Год журнала: 2024, Номер 199, С. 115989 - 115989
Опубликована: Янв. 2, 2024
Язык: Английский
Процитировано
2
Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)
Опубликована: Май 1, 2024
Primary testicular lymphoma (PTL) is a rare predominantly occurring in the elderly male population. It characterized by limited response to treatment and heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features were delineated scope within several independent studies. Some articles which analyzed genetic characterization DLBCL have incorporated samples, but these been constrained small sample sizes. In addition, there an absence molecular typing studies PTL. This report summarizes common mutational features, copy number variations (CNVs) patients, based on whole-exome sequencing (WES) conducted cohort 25 patients. Among them, HLA, CDKN2A MYD88 had high mutation frequency. we found two core characteristics including genes linked genomic instability (TP53 CDKN2A) immune-related (HLA, MYD88, CD79B). We performed patients into C1 subtype with TP53 mutations C2 HLA mutations. Notably, gene predicted poor outcome most types lymphomas. However, subtype, dominated mutations, better prognosis compared exhibited worse prognosis, aligning our finding that mechanism immune escape was primarily deletions rather than PD-L1/PD-L2 alterations, contrast other DLBCLs. Moreover, calculated tumor burden (TMB) identified TMB can predict recurrence rate Our study underscores significance characteristics, plays crucial role prognostication guiding therapeutic strategies for
Язык: Английский
Процитировано
2