【目的】探究原肌球蛋白(tropomyosin,TM)是否在猪背最长肌生长发育过程中发挥生物学功能。【方法】采用SYBR Green Ⅱ荧光法进行荧光定量PCR分析TPM1基因在通城猪和长白猪中的组织表达谱,以及出生前和出生后背最长肌发育中(28个发育...【目的】探究原肌球蛋白(tropomyosin,TM)是否在猪背最长肌生长发育过程中发挥生物学功能。【方法】采用SYBR Green Ⅱ荧光法进行荧光定量PCR分析TPM1基因在通城猪和长白猪中的组织表达谱,以及出生前和出生后背最长肌发育中(28个发育点)的表达变化。【结果】TPM1基因在两种猪中背肌和心肌中都有丰富地表达,在背最长肌发育过程中的表达趋势相似,即TPM1基因的表达量先增加后减少,但出现峰值的时间不同(通城猪中,TPM1基因在胚胎期75 d的表达量显著高于其它时间点,P<0.05;长白猪中,TPM1基因在胚胎期90 d的表达量显著高于其它时间点,P<0.05)。【结论】TPM1基因的表达与猪背最长肌生长发育及品种间肌肉表型差异有关。展开更多
Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality worldwide.The prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic response.Ho...Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality worldwide.The prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic response.However,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be elusive.In this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free interval.Upregulation of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their stemness.RNA pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a compound.UBA1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination modification.Methylated RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A methylation.Furthermore,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in vivo.Collectively,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.展开更多
文摘【目的】探究原肌球蛋白(tropomyosin,TM)是否在猪背最长肌生长发育过程中发挥生物学功能。【方法】采用SYBR Green Ⅱ荧光法进行荧光定量PCR分析TPM1基因在通城猪和长白猪中的组织表达谱,以及出生前和出生后背最长肌发育中(28个发育点)的表达变化。【结果】TPM1基因在两种猪中背肌和心肌中都有丰富地表达,在背最长肌发育过程中的表达趋势相似,即TPM1基因的表达量先增加后减少,但出现峰值的时间不同(通城猪中,TPM1基因在胚胎期75 d的表达量显著高于其它时间点,P<0.05;长白猪中,TPM1基因在胚胎期90 d的表达量显著高于其它时间点,P<0.05)。【结论】TPM1基因的表达与猪背最长肌生长发育及品种间肌肉表型差异有关。
基金grants from the National Natural Science Foundation of China(81802554 and 32170862)the Experimental Animal Fund of Shanghai Science and Technology Commission(22140903800)a Project Funded by China Postdoctoral Science Foundation(2021M692432).
文摘Prostate cancer(PCa)is a common malignant tumor with high morbidity and mortality worldwide.The prostate cancer stem cell(PCSC)model provides novel insights into the pathogenesis of PCa and its therapeutic response.However,the roles and molecular mechanisms of specific genes in mediating fate decisions of PCSCs and carcinogenesis of PCa remain to be elusive.In this study,we have explored the expression,function,and mechanism of AZGP1P2,a pseudogene of AZGP1,in regulating the stemness and apoptosis of PCSCs and treatment resistance of docetaxel in castration-resistant prostate cancer(CRPC).We revealed that AZGP1P2 was downregulated in CRPC cell lines and PCSCs,while it was positively associated with progression-free interval.Upregulation of the AZGP1P2 enhanced the sensitivity of docetaxel treatment in CRPCs via inhibiting their stemness.RNA pull-down associated with mass spectrometry analysis,co-immunoprecipitation assay,and RNA immunoprecipitation assay demonstrated that AZGP1P2 could bind to UBA1 and RBM15 as a“writer”of methyltransferase to form a compound.UBA1,an E1 ubiquitin-activating enzyme,contributed to RBM15 protein degradation via ubiquitination modification.Methylated RNA immunoprecipitation assay displayed that RBM15 controlled the mRNA decay of TPM1 in m6A methylation.Furthermore,a xenograft mouse model and patient-derived organoids showed that the therapeutic effect of docetaxel in CRPC was increased by AZGP1P2 in vivo.Collectively,these results imply that AZGP1P2 mediates the stemness and apoptosis of PCSCs and promotes docetaxel therapeutic effect by suppressing tumor growth and metastasis via UBA1/RBM15-mediated TPM1 mRNA decay in CRPC.
