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ABSTRACT Background: The depth of response to platinum in urothelial neoplasm tissues varies greatly. Biomarkers that have practical value in prognosis stratification are increasingly needed. Our study aimed to select a set of BC (bladder cancer)-related genes involved in both platinum resistance and survival, then use these genes to establish the prognostic model. Materials and Methods: Platinum resistance-related DEGs (differentially expressed genes) and tumorigenesis-related DEGs were identified. Ten most predictive co-DEGs were acquired followed by building a risk score model. Survival analysis and ROC (receiver operating characteristic) plot were used to evaluate the predictive accuracy. Combined with age and tumor stages, a nomogram was generated to create a graphical representation of survival rates at 1-, 3-, 5-, and 8-year in BC patients. The prognostic performance was validated in three independent BC datasets with platinum-based chemotherapy. The potential mechanism was explored by enrichment analysis. Results: PPP2R2B, TSPAN7, ATAD3C, SYT15, SAPCD1, AKR1B1, TCHH, AKAP12, AGLN3, and IGF2 were selected for our prognostic model. Patients in high- and low-risk groups exhibited a significant survival difference with HR (hazard ratio) = 2.7 (p < 0.0001). The prognostic nomogram of predicting 3-year OS (overall survival) for BC patients could yield an AUC (area under the curve) of 0.819. In the external validation dataset, the risk score also has a robust predictive ability. Conclusion: A prognostic model derived from platinum resistance-related genes was constructed, we confirmed its value in predicting platinum-based chemotherapy benefits and overall survival for BC patients. The model might assist in therapeutic decisions for bladder malignancy.
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ABSTRACTPurpose:RNA activation (RNAa) is a mechanism of gene activation triggered by promoter-targeted small double stranded RNAs (dsRNAs), also known as small activating RNAs (saRNAs). Myogenic regulatory factor MyoD is regarded as the master activator of myogenic differentiation cascade by binding to enhancer of muscle specific genes. Stress urinary incontinence (SUI) is a condition primarily resulted from urethral sphincter deficiency. It is thus expected that by promoting differentiation of adipose-derived stem cells (ADSCs) into myoblasts by activating MyoD gene through RNAa may offer benefits to SUI.Materials and Methods:Rats ADSCs were isolated, proliferated in vitro, and identified by flow cytometry. Purified ADSCs were then transfected with a MyoD saRNA or control transfected. Real-time polymerase chain reaction (RT-PCR) and western blotting were used to detect MyoD mRNA and protein expression, respectively. Immunocytochemical staining was applied to determine the expression of desmin protein in transfected cells. Cell viability was measured by using CellTiter 96® AQueous One Solution Cell Proliferation Assay kit.Results:Transfection of a MyoD saRNA (dsMyoD) into ADSCs significantly induced the expression of MyoD at both the mRNA and protein levels, and inhibited cell proliferation. Desmin protein expression was detected in dsMyoD treated ADSCs 2 weeks later.Conclusion:Our findings show that RNAa mediated overexpression of MyoD can promote transdifferentiation of ADSCs into myoblasts and may help treat stress urinary incontinence (SUI)–a condition primarily resulted from urethral sphincter deficiency.