ABSTRACT
BACKGROUND: The aim of this study was to investigate the biological functions and underlying mechanisms of SIRT5 in clear cell renal cell carcinoma (ccRCC). METHODS: SIRT5 expression data in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) were selected, and the correlations between SIRT5 expression and various clinicopathological parameters were analysed. SIRT5 expression in ccRCC tissues was examined using immunohistochemistry. Stable cell lines with SIRT5 knockdown were established. In vitro and in vivo experiments were conducted to investigate the functional roles of SIRT5 in the cellular biology of ccRCC, including cell viability assays, wound healing assays, soft agar colony formation assays, Transwell invasion assays, qRT-PCR, and Western blotting. In addition, microarrays, rescue experiments and Western blotting were used to investigate the molecular mechanisms underlying SIRT5 functions. RESULTS: SIRT5 expression was downregulated in ccRCC compared with normal tissues, which correlated with a poor prognosis of ccRCC. SIRT5 knockdown significantly increased cell proliferation, migration and invasion in vitro. In vivo experiments revealed that SIRT5 knockdown promoted ccRCC tumorigenesis and metastasis. Mechanistically, SIRT5 deglycosylated PDHA1 at K351 and increased PDC activity, thereby altering the metabolic crosstalk with the TCA cycle and inhibiting the Warburg effect. SIRT5 overexpression was related to low succinylation of PDHA1. CONCLUSIONS: Downregulated SIRT5 expression in ccRCC accelerated the Warburg effect through PDHA1 hypersuccinylation and induced tumorigenesis and progression, indicating that SIRT5 may become a potential target for ccRCC therapy.
Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Sirtuins , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Genes, Tumor Suppressor , Humans , Kidney Neoplasms/pathology , Sirtuins/genetics , Sirtuins/metabolismABSTRACT
Objective:To analyze the predictive factors of GGU between biopsy and radical prostatectomy pathology based on 2014 ISUP grouping system, then establish and evaluate nomogram.Methods:Patients undergoing radical prostatectomy in Shanghai Ruijin Hospital from March 2012 to March 2019 were reviewed, and the clinical and pathological information were collected. Age(68.1±7.2), body mass indes(BMI) (24.2±3.2)kg/m 2, prostate specific antigen(PSA) 11.5(6.7-20.4)ng/ml, prostate specific antigen destiny(PSAD) 0.35(0.20-0.66). Before March 2017, the number of biopsy cores were 6 to 8; After then, all patients toke 12 cores systemic biopsy. Based on 2014 ISUP grouping system, the differences between biopsy and radical prostatectomy grades were counted. The independent predictors of GGU were analyzed by univariate and multivariate logistic regression analysis, then the nomogram for predicting GGU were established and evaluated. Results:429 patients were enrolled. There were 161 (37.5%) patients in GGU group and 268 (62.5%) patients in non-GGU group. After multivariate logistic regression analysis, body mass index (BMI)>28 kg/m 2( OR=2.54, P=0.021), prostate specific antigen density (PSAD)( OR=1.65, P=0.018)and 2014 ISUP grouping sysyem ( OR=0.53, P<0.001) of biopsy specimen were independent impact factors of GGU. The predicting model was established according to BMI, PSAD and 2014 ISUP grouping system. The area under the ROC cure of the model was 0.735 (95% CI 0.681-0.789). The nomogram model was well calibrated, with the mean absolute error of 6.7%, which means the prediction of GGU is fairly consistent with the actual situation. Conclusions:Based on the 2014 ISUP grouping system, BMI>28 kg/m 2, PSAD and 2014 ISUP grouping of biopsy specimen were independent predictors of GGU. The nomogram model for predicting GGU has a good statistical significance.
ABSTRACT
Alginate fiber is prepared by wet spinning method.The preparation process of alginate fiber is:dissolution,filtration,deaeration,figuration,stretching,washing,drying and convoluting.At present,one of thebiodegradable fibers studied the most is alginate fiber.The material,principle and producing technology of alginatefibers are introduced in this article and its application in wound dressings are underlined.
