目的泛癌分析长链非编码RNA(lncRNA)MIR22HG的表达及其与临床特征的关系。方法R语言分析癌症基因组图谱(TCGA)中MIR22HG在不同肿瘤组织中的表达及其与临床分期、淋巴结转移、肿瘤突变负荷(TMB)及微卫星不稳定(MSI)的关系;应用TIMER比较M...目的泛癌分析长链非编码RNA(lncRNA)MIR22HG的表达及其与临床特征的关系。方法R语言分析癌症基因组图谱(TCGA)中MIR22HG在不同肿瘤组织中的表达及其与临床分期、淋巴结转移、肿瘤突变负荷(TMB)及微卫星不稳定(MSI)的关系;应用TIMER比较MIR22HG表达与免疫浸润的关系;使用cBioPortal分析MIR22HG的突变频率及其与预后的关系;使用GDSC在线数据库分析MIR22HG与化疗药物敏感性的关系。利用GEO数据库肝癌数据集和12对肝癌标本验证MIR22HG在肝癌中的表达及其与索拉非尼治疗反应的关系;分析MIR22HG表达与索拉非尼治疗预后的关系;在肝癌细胞株HCC-LM3中过表达MIR22HG(NC组,MIR22HG过表达组),在肝癌细胞株MHCC-97H中敲除MIR22HG(NC组,sh-MIR22HG组),采用CCK-8检测肝癌细胞中MIR22HG对索拉非尼IC_(50)的影响。结果MIR22HG在大多数肿瘤中低表达(P<0.05),且多数肿瘤中MIR22HG基因存在缺失突变,其突变与肿瘤不良预后相关(P<0.05)。MIR22HG的表达水平与多种肿瘤的临床分期及淋巴结转移相关(P<0.05)。在多种肿瘤中MIR22HG的表达水平与TBM、MSI、免疫评分、免疫检查点相关基因表达及化疗药的药物敏感性显著相关(P<0.05)。6种常见免疫细胞中,中性粒细胞浸润水平与MIR22HG的表达水平相关性最强,尤其在乳腺癌、直肠癌及肾乳头状细胞癌中明显。多个数据集的分析结果验证MIR22HG在肝癌中低表达,且其低表达与肝癌进展相关(P<0.05)。MIR22HG低表达的患者经索拉非尼治疗后预后较好(HR=2.94,P=0.075),其低表达能有效预测肝癌患者索拉非尼治疗效果(AUC=0.8095)。过表达MIR22HG能降低肝癌细胞对索拉非尼的敏感性(IC_(50 NC) vs IC_(50 MIR22HG)=7.731 vs 15.61);而敲除MIR22HG的表达则能增加肝癌细胞对索拉非尼的敏感性(IC_(50 NC) vs IC50sh-MIR22HG=7.986 vs 5.085)。结论MIR22HG的表达与多种肿瘤的分期、有否淋巴结转移、肿瘤突变负荷、微卫星不稳定、免疫细胞浸润及化疗药物敏感性相关。展开更多
Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life....Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.展开更多
文摘目的泛癌分析长链非编码RNA(lncRNA)MIR22HG的表达及其与临床特征的关系。方法R语言分析癌症基因组图谱(TCGA)中MIR22HG在不同肿瘤组织中的表达及其与临床分期、淋巴结转移、肿瘤突变负荷(TMB)及微卫星不稳定(MSI)的关系;应用TIMER比较MIR22HG表达与免疫浸润的关系;使用cBioPortal分析MIR22HG的突变频率及其与预后的关系;使用GDSC在线数据库分析MIR22HG与化疗药物敏感性的关系。利用GEO数据库肝癌数据集和12对肝癌标本验证MIR22HG在肝癌中的表达及其与索拉非尼治疗反应的关系;分析MIR22HG表达与索拉非尼治疗预后的关系;在肝癌细胞株HCC-LM3中过表达MIR22HG(NC组,MIR22HG过表达组),在肝癌细胞株MHCC-97H中敲除MIR22HG(NC组,sh-MIR22HG组),采用CCK-8检测肝癌细胞中MIR22HG对索拉非尼IC_(50)的影响。结果MIR22HG在大多数肿瘤中低表达(P<0.05),且多数肿瘤中MIR22HG基因存在缺失突变,其突变与肿瘤不良预后相关(P<0.05)。MIR22HG的表达水平与多种肿瘤的临床分期及淋巴结转移相关(P<0.05)。在多种肿瘤中MIR22HG的表达水平与TBM、MSI、免疫评分、免疫检查点相关基因表达及化疗药的药物敏感性显著相关(P<0.05)。6种常见免疫细胞中,中性粒细胞浸润水平与MIR22HG的表达水平相关性最强,尤其在乳腺癌、直肠癌及肾乳头状细胞癌中明显。多个数据集的分析结果验证MIR22HG在肝癌中低表达,且其低表达与肝癌进展相关(P<0.05)。MIR22HG低表达的患者经索拉非尼治疗后预后较好(HR=2.94,P=0.075),其低表达能有效预测肝癌患者索拉非尼治疗效果(AUC=0.8095)。过表达MIR22HG能降低肝癌细胞对索拉非尼的敏感性(IC_(50 NC) vs IC_(50 MIR22HG)=7.731 vs 15.61);而敲除MIR22HG的表达则能增加肝癌细胞对索拉非尼的敏感性(IC_(50 NC) vs IC50sh-MIR22HG=7.986 vs 5.085)。结论MIR22HG的表达与多种肿瘤的分期、有否淋巴结转移、肿瘤突变负荷、微卫星不稳定、免疫细胞浸润及化疗药物敏感性相关。
基金This study was financially supported by grants from the National Natural Science Foundation of China(82071119,82071142,81700938,81772876,81800942).
文摘Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.
