目的通过Meta分析评估血液中lncRNA HAND2反义RNA1(HAND2-AS1)的表达水平对多种肿瘤的临床诊断价值。方法由两名评价员利用计算机检索PubMed、Embase、SinoMed和万方等数据库,检索时限为1980年1月1日至2020年9月30日,收集国内外公开发...目的通过Meta分析评估血液中lncRNA HAND2反义RNA1(HAND2-AS1)的表达水平对多种肿瘤的临床诊断价值。方法由两名评价员利用计算机检索PubMed、Embase、SinoMed和万方等数据库,检索时限为1980年1月1日至2020年9月30日,收集国内外公开发表有关HAND2-AS1表达水平与肿瘤癌症相关的所有文献,采用STATA 14.0软件对数据进行Meta分析。结果严格按照纳入和排除标准,筛选出6篇文献进行Meta分析,包括317名肿瘤患者和227名健康对照者。连续型变量所合并的效应量为标准化均数差(Standardized mean difference,SMD),具体为[SMD=-1.61,95%CI(-1.80,-1.41),P<0.00001]。对于HAND2-AS1的诊断价值,汇总敏感度、特异度分别为0.87和0.82,诊断比值比(Diagnostic Odds Ratio,DOR)为32,综合受试者工作特征曲线的曲线下面积(Aarea under curve,AUC)为0.91。结论血液中HAND2-AS1的检测在多种肿瘤的诊断中具有较高的敏感度和特异度,对区分患者和健康个体具有较高的临床诊断价值。展开更多
Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus...Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.展开更多
目的探究乳腺癌源性LncRNA OIP5-AS1经肿瘤相关巨噬细胞(TAM)M2型极化调控乳腺癌细胞迁移、侵袭及上皮—间质转化的机制。方法MDA-MB-231细胞分设Control组(空白对照)、NC组(转染NC si RNA)和si-OIP5组(转染Lnc RNAOIP5-AS1 si RNA)。RT...目的探究乳腺癌源性LncRNA OIP5-AS1经肿瘤相关巨噬细胞(TAM)M2型极化调控乳腺癌细胞迁移、侵袭及上皮—间质转化的机制。方法MDA-MB-231细胞分设Control组(空白对照)、NC组(转染NC si RNA)和si-OIP5组(转染Lnc RNAOIP5-AS1 si RNA)。RT-qPCR检测Lnc RNA OIP5-AS1、IL-4和IL-13 m RNA表达;ELISA检测培养基上清IL-4和IL-13蛋白表达。Control组培养上清按不同体积比加入RPMI1640培养基中诱导M0巨噬细胞向TAM极化,RT-qPCR检测TAM中CD206 m RNA的表达;以NC组/si-OIP5组培养基上清诱导M0型巨噬细胞,Western blot检测CD206表达;继而构建巨噬细胞MDA-MB-231共培养模型,评估MDAMB-231细胞迁移侵袭能力并检测Vimentin、N-cadherin、Ecadherin表达变化。结果相较于Control及NC组,si-OIP5组Lnc RNAOIP5-AS1表达显著下调(P<0.001),IL-13m RNA及蛋白水平均显著降低(P<0.05),而IL-4表达在各组间无明显差异。条件培养基呈体积依赖性诱导M0巨噬细胞CD206表达,40%体积比时效应最强(P<0.001)。相较NC组,si-OIP5组CD206蛋白水平显著降低(P<0.01)。共培养体系中,si-OIP5组MDA-MB-231细胞迁移侵袭能力显著减弱(P<0.001),E-cadherin表达上调,N-cadherin及Vimentin表达下调(均P<0.01)。结论乳腺癌源性Lnc RNA OIP5-AS1可经IL-13介导诱导TAM M2型极化,进而促进乳腺癌细胞的迁移、侵袭及EMT。展开更多
文摘目的通过Meta分析评估血液中lncRNA HAND2反义RNA1(HAND2-AS1)的表达水平对多种肿瘤的临床诊断价值。方法由两名评价员利用计算机检索PubMed、Embase、SinoMed和万方等数据库,检索时限为1980年1月1日至2020年9月30日,收集国内外公开发表有关HAND2-AS1表达水平与肿瘤癌症相关的所有文献,采用STATA 14.0软件对数据进行Meta分析。结果严格按照纳入和排除标准,筛选出6篇文献进行Meta分析,包括317名肿瘤患者和227名健康对照者。连续型变量所合并的效应量为标准化均数差(Standardized mean difference,SMD),具体为[SMD=-1.61,95%CI(-1.80,-1.41),P<0.00001]。对于HAND2-AS1的诊断价值,汇总敏感度、特异度分别为0.87和0.82,诊断比值比(Diagnostic Odds Ratio,DOR)为32,综合受试者工作特征曲线的曲线下面积(Aarea under curve,AUC)为0.91。结论血液中HAND2-AS1的检测在多种肿瘤的诊断中具有较高的敏感度和特异度,对区分患者和健康个体具有较高的临床诊断价值。
基金supported by the Natural Science Foundation of Hubei Province of China(Grant No.2023AFB671)the National Natural Science Foundation of China(Grant Nos.82360177 and 82560182)+1 种基金the Key Project of Jiangxi Provincial Natural Science Foundation(Grant No.20224ACB206011)“Xuncheng Talents”Project in Jiujiang City,Jiangxi Province(Grant No.JJXC2023071).
文摘Objectives The discovery of novel molecular targets to enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells(H-BMSCs)represents a promising strategy for preventing and treating osteoporosis.Thus,the primary objective of this study is to elucidate the mechanisms by which long non-coding RNA FOXD2-AS1(lncRNA FOXD2-AS1)regulates early osteogenic differentiation in H-BMSCs,thereby identifying potential therapeutic targets.Methods Lentivirus-mediated vectors were constructed to either overexpress or silence FOXD2-AS1 in H-BMSCs.The effects of FOXD2-AS1 on osteogenesis were subsequently assessed by analyzing osteogenic marker expression and alkaline phosphatase(ALP)staining.To clarify the role of the Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3)pathway in this process,AG490 inhibitor(a JAK2/STAT3 pathway inhibitor)and knockdown of STAT3 were used to investigate the mechanisms of FOXD2-AS1.Results FOXD2-AS1 overexpression increased ALP activity and osteogenic marker expression,while its knockdown had the opposite effects.From a mechanistic perspective,FOXD2-AS1 overexpression promoted JAK2 and STAT3 phosphorylation,whereas its suppression attenuated their activation.Also,the osteogenic increase induced by FOXD2-AS1 overexpression was reversed by AG490 treatment or STAT3 silencing,indicating that the pathway plays a role in this process.Conclusion FOXD2-AS1 was identified as a novel genetic switch driving osteogenic commitment via JAK2/STAT3 activation,revealing a new regulatory mechanism and a potential therapeutic target for osteoporosis.
文摘目的探究乳腺癌源性LncRNA OIP5-AS1经肿瘤相关巨噬细胞(TAM)M2型极化调控乳腺癌细胞迁移、侵袭及上皮—间质转化的机制。方法MDA-MB-231细胞分设Control组(空白对照)、NC组(转染NC si RNA)和si-OIP5组(转染Lnc RNAOIP5-AS1 si RNA)。RT-qPCR检测Lnc RNA OIP5-AS1、IL-4和IL-13 m RNA表达;ELISA检测培养基上清IL-4和IL-13蛋白表达。Control组培养上清按不同体积比加入RPMI1640培养基中诱导M0巨噬细胞向TAM极化,RT-qPCR检测TAM中CD206 m RNA的表达;以NC组/si-OIP5组培养基上清诱导M0型巨噬细胞,Western blot检测CD206表达;继而构建巨噬细胞MDA-MB-231共培养模型,评估MDAMB-231细胞迁移侵袭能力并检测Vimentin、N-cadherin、Ecadherin表达变化。结果相较于Control及NC组,si-OIP5组Lnc RNAOIP5-AS1表达显著下调(P<0.001),IL-13m RNA及蛋白水平均显著降低(P<0.05),而IL-4表达在各组间无明显差异。条件培养基呈体积依赖性诱导M0巨噬细胞CD206表达,40%体积比时效应最强(P<0.001)。相较NC组,si-OIP5组CD206蛋白水平显著降低(P<0.01)。共培养体系中,si-OIP5组MDA-MB-231细胞迁移侵袭能力显著减弱(P<0.001),E-cadherin表达上调,N-cadherin及Vimentin表达下调(均P<0.01)。结论乳腺癌源性Lnc RNA OIP5-AS1可经IL-13介导诱导TAM M2型极化,进而促进乳腺癌细胞的迁移、侵袭及EMT。
