RESUMO
Neuropathic pain (NP) caused by nerve injury or dysfunction is one of the most challenging neurological diseases. In-depth study of disease signatures contributes to the development of novel target treatment for NP. In this study, we analyzed expression profiles of qualified NP datasets (GSE24982 and GSE63442) deposited at Gene Expression Omnibus database by systematic bioinformatics approaches. We analyzed the differentially expressed genes of high and low pain compared with normal control group, and between spinal nerve ligation (SNL) injury model and sham-operation group. A total of 1,243 upregulated and 1,533 downregulated genes were identified in GSE24982, 380 upregulated and 355 downregulated genes were identified in GSE63442. By comparing low-pain samples with the corresponding sham-operation group, we identified 457 upregulated and 409 downregulated genes. Overlapping genes were screened out and signaling pathway and expression regulation model analyses were performed. SCN10A and SST were identified as biomarkers for NP. In conclusion, our study showed the expression pattern of gene about NP. These identified biomarkers could serve as potential therapeutic targets for treating NP.
Assuntos
Redes Reguladoras de Genes/genética , Canal de Sódio Disparado por Voltagem NAV1.8/genética , Neuralgia/genética , Somatostatina/genética , Biomarcadores/análise , Biologia Computacional , Feminino , Regulação da Expressão Gênica/genética , Ontologia Genética , Humanos , Masculino , Neuralgia/patologia , Neuralgia/terapia , Mapas de Interação de Proteínas/genética , Transdução de Sinais/genética , Medula Espinal/metabolismo , Medula Espinal/patologiaRESUMO
Renal cell carcinoma is one of the most common kidney cancer, which accounts almost 90% of the adult renal malignancies worldwide. In recent years, a new class of endogenous noncoding RNAs, circular RNAs, exert important roles in cell function and certain types of pathological responses, especially in cancers, generally by acting as a microRNA sponge. Circular RNAs could act as sponge to regulate the microRNA and the target genes. However, the knowledge about circular RNAs in renal cell carcinoma remains unclear so far. In the research, we selected a highly expressed novel circular RNAs named circMTO1 in renal cell carcinomas. We investigated the roles of circMTO1 and found that circMTO1 overexpression could suppress cell proliferation and metastases in both A497 and 786-O renal cancer cells, while silencing of circMTO1 could promote the progression in SN12C and OS-RC-2 renal cancer cells. The study showed that circMTO1 acted as miR9 and miR223 sponge and inhibited their levels. Furthermore, silencing of circMTO1 in renal cell carcinoma could downregulate LMX1A, the target of miR-9, resulting in the promotion of renal cell carcinoma cell proliferation and invasion. In addition, LMX1A expression suppression induced by transfection of miR9 mimics confirmed that miR9 exerted its function in renal cell carcinoma by regulating LMX1A expression. What's more, miR9 inhibitor and LMX1A overexpression could block the tumor-promoting effect of circMTO1 silencing. In conclusion, circMTO1 suppresses renal cell carcinoma progression by circMTO1/miR9/ LMX1A, indicating that circMTO1 may be a potential target in renal cell carcinoma therapy.
Assuntos
Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Proteínas com Homeodomínio LIM/metabolismo , MicroRNAs/metabolismo , RNA Circular/genética , Fatores de Transcrição/metabolismo , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Progressão da Doença , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas com Homeodomínio LIM/genética , MicroRNAs/genética , RNA Circular/metabolismo , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Cellular immunotherapies, such as chimeric antigen receptor modified-T cell (CAR-T) therapy, offers excellent potential for tumor treatment. The memory phenotype of CAR-T has been correlated positively with a therapeutic effect on and prognosis of cancer. METHOD: The proliferation rates of novel CAR-T was determined by cell counting. The phenotypes of CAR-T cells were then detected by flow cytometry. The cell cytotoxicity against tumor cells in vitro was investigated by lactate dehydrogenase assay and luciferase assay. The cytokines secreted during these assays were determined by the cytometric bead array assay. The antitumor ability in vivo was evaluated in NOG mice. RESULTS: Co-expression of an LRP6 full-length protein with anti-CD19 CAR significantly improved the memory phenotype of CAR-positive T-cells by enhancing the wnt signaling pathway. As compared with anti-CD19 CAR-T, anti-CD19 CAR-T-LRP6 exhibited more robust cytotoxicity against tumor cells in vitro and in vivo, albeit fewer cytokines were released in vitro. Moreover, the longer survival rate and robust expansion in vivo of anti-CD19 CAR-T-LRP6 cells were found to be effective in inhibiting cancer recurrence. CONCLUSIONS: CAR co-expressed with LRP6 could sustain the memory phenotype that enabled permanent relief and may further assist in the development of potent and durable T-cell therapeutics.