RESUMO
BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin lymphoma with high mortality rates. Small nucleolar RNAs (snoRNAs) are tumor-specific biological markers, but there are few studies on the role of snoRNAs in DLBCL. MATERIALS AND METHODS: Survival-related snoRNAs were selected to construct a specific snoRNA-based signature via computational analyses (Cox regression and independent prognostic analyses) to predict the prognosis of DLBCL patients. To assist in clinical applications, a nomogram was built by combining the risk model and other independent prognostic factors. Pathway analysis, gene ontology analysis, transcription factor enrichment, protein-protein interactions, and single nucleotide variant analysis were used to explore the potential biological mechanisms of co-expressed genes. RESULTS: Twelve prognosis-correlated snoRNAs were selected from the DLBCL patient cohort of microarray profiles, and a three-snoRNA signature consisting of SNORD1A, SNORA60, and SNORA66 was constructed. DLBCL patients could be divided into high-risk and low-risk cohorts using the risk model, and the high-risk group and activated B cell-like (ABC) type DLBCL were linked with disappointing survival. In addition, SNORD1A co-expressed genes were inseparably linked to the biological functions of the ribosome and mitochondria. Potential transcriptional regulatory networks have also been identified. MYC and RPL10A were the most mutated SNORD1A co-expressed genes in DLBCL. CONCLUSION: Put together, our findings explored the potential biological effects of snoRNAs in DLBCL, and provided a new predictor for DLBCL prediction.
Assuntos
Linfoma Difuso de Grandes Células B , RNA Nucleolar Pequeno , Humanos , Prognóstico , Linfócitos B/patologia , Nomogramas , Biomarcadores Tumorais/genéticaRESUMO
BACKGROUND: Traditional chemotherapy has benefited many patients with non-Hodgkin's lymphoma, but results in a very poor response in patients with rare lymphomas or refractory lymphomas. Previous studies have shown that chidamide has potential anti-lymphoma activity and reverses lymphoma cell chemoresistance to increase the chemosensitivity of lymphoma cells to traditional chemotherapy. CASE SUMMARY: A 14-year-old boy was admitted to our hospital with a 5-d history of generalized erythema, papules, and blisters. Initially, the disease was refractory to potent anti-allergic and anti-infective treatment, and his condition progressively worsened. Skin biopsy revealed primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Considering that the disease is extremely rare in clinical practice, existing case reports have shown poor efficacy with traditional chemotherapy alone. We recommend chidamide combined with traditional chemotherapy for treatment. The regimen was as follows: Chidamide 30 mg/biw, cyclophosphamide 1100 mg/d1, pirarubicin 70 mg/d1, vincristine 2 mg/d1, dexamethasone 20 mg/d1-5, etoposide 100 mg/d1-5, in a 21 d cycle. The treatment effect was considerable, and complete remission was achieved after 4 cycles of treatment, after which the patient completed a total of 6 cycles of treatment. Subsequently, the patient regularly took chidamide 20 mg/biw as maintenance therapy for 1 year. To date, the patient has been disease-free for 3 years. CONCLUSION: This case suggests that the combination of chidamide and traditional chemotherapy is effective in primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma.
RESUMO
The aim of the present study was to determine the effect of the long noncoding RNA (lncRNA) bladder cancerassociated transcript 1 (BLACAT1) in chemoresistance of nonsmall cell lung cancer (NSCLC) cells. Expression of lncRNA BLACAT1, microRNA (miR)17, autophagyrelated protein 7 (ATG7), multidrugresistance protein 1 (MRP1), and the autophagyassociated proteins light chain 3 (LC3)II/LC3I and Beclin 1 were detected using the reverse transcriptionquantitative polymerase chain reaction and western blot analysis. Cell viability was determined using an MTT assay. The interaction between BLACAT1 and miR17 was determined using RNA immunoprecipitation and RNA pulldown assays. A cisplatin (DDP)resistant NSCLC cell A549/DDP xenograft model in nude mice was established to investigate the effect of BLACAT1 on the chemoresistance of NSCLC cells. Compared with in DDPsensitive NSCLC cells, expression of BLACAT1, ATG7, MRP1, LC3II/LC3I and Beclin 1 was significantly upregulated in DDPresistant NSCLC cells, whereas miR17 was downregulated in DDPresistant NSCLC cells. Short interfering RNA against BLACAT1 decreased the viability of DDPresistant NSCLC cells. In addition, BLACAT1 interacted with miR17, and negatively regulated miR17. BLACAT1 promoted ATG7 expression through miR17, and facilitated autophagy and promoted chemoresistance of NSCLC cells through miR17/ATG7. Finally, in vivo experiments indicated that inhibition of BLACAT1 ameliorated the chemoresistance of NSCLC. BLACAT1 was upregulated in DDPresistant NSCLC cells, and promoted autophagy and chemoresistance of NSCLC cells through the miR17/ATG7 signaling pathway.
Assuntos
Proteína 7 Relacionada à Autofagia/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Células A549 , Animais , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Cisplatino/uso terapêutico , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Transplante de Neoplasias , Transdução de SinaisRESUMO
Recent studies have shown that Beclin 1, a key regulator of autophagic process, is frequently downregulated and may serve as an independent prognostic biomarker for nonsmall cell lung cancer. However, the molecular mechanisms underlying its downregulation remain poorly understood. The signal transducer and activator of transcription 3 (Stat3) is a transcription factor which plays a crucial role for multiple tumor growth and progression. Here, we demonstrate that Beclin 1 is a direct transcriptional target of Stat3 in lung cancer cells. Interleukin-6 (IL-6) treatment or transfection of a constitutively activated Stat3 in AGS and NCI-H1650 cells inhibited Beclin 1 expression. At the molecular level, we further revealed that Stat3 could directly bind to the promoter region of Beclin 1 and repressed its transcription through recruiting histone deacetylase 3 (HDAC3). Collectively, our results suggest that the activated Stat3 may represent an important mechanism for Beclin 1 downregulation in nonsmall cell lung cancer development.