The present study investigated the role and molecular mechanism of long non-coding rna (lncrna) metastasis associated lung adenocarcinoma transcript (MalaT)1 in neuropathic pain in rat chronic constriction injury (cci) model. reverse transcription-quantitative Pcr and western blot analysis were used to detect the expression levels of MalaT1, microrna (mir)-154-5p and aquaporin (aQP)9 in spinal cord tissue and microglia of cci rats. eliSa and pain behavioral assays were used to observe the effect of MalaT1 on neuropathic pain and neuroinflammation in model rats, and to verify its molecular mechanism through bioinformatics and luciferase experiments. The results of the present study identified that the expression levels of MALAT1 and AQP9 were upregulated, while mir-154-5p was downregulated in spinal cord tissue and microglia of cci rats. MalaT1 knockdown in CCI model rats significantly induced the occurrence of neuropathic pain, while the upregulation of mir-154-5p could reverse this process. The present study also identified that miR-154-5p was the target gene of MALAT1, and aQP9 was the target gene of mir-154-5p. aQP9 knockdown promoted the occurrence of neuropathic pain. in conclusion, lncrna MalaT1 promotes the progression of neuropathic pain in rats by reducing mir-154-5p and increasing aQP9. The MalaT1/mir-154-5p/aQP9 axis can be used as a new therapeutic target for neuropathic pain.
Background: Papillary renal cell carcinoma (PRCC) is the second most prevalent subtype of renal cell carcinoma (RCC), accounting for 15% of all RCCs. Tumor mutational burden (TMB) is a promising prognostic factor in many types of cancers. The present study aimed to investigate the association between TMB and patient survival in PRCC patients.Methods: Genomic and clinical data of 281 PRCC patients were collected from The Cancer Genome Atlas. Overall survival (OS) was compared between patients with high and low TMB using the Kaplan-Meier method with log-rank tests. Gene expression comparison and immune cell fraction comparison were performed using Student’s t test or Wilcoxon’s rank-sum test. Results: Patients with high TMB tumors had longer OS than those with low TMB tumors. Among tumor-infiltrating immune cells, high TMB tumors were associated with high levels of CD4+ T-cell infiltration, which were further associated with better survival. Furthermore, low TMB tumors were associated with a high level of infiltration of regulatory T-cells and dendritic cells. Among immune checkpoint genes, low TMB tumors expressed high levels of CD274, PDCD1LG2, LAG3, and TGFB1, and these genes were associated with a poor prognosis in PRCC. Among cytokine-related genes, low TMB tumors were associated with a high expression of IL6, whereas high TMB tumors were associated with a high expression of IFNA1.Conclusions: High TMB indicated better survival outcomes in PRCC patients. High TMB was associated with anti-tumor immune cell infiltration, whereas low TMB was associated with high expression of checkpoint genes that indicated a worse prognosis in RCC. Moreover, TMB was associated with the expression of immune cytokines. Thus, TMB may be a novel prognostic factor in PRCC.
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