钙激活氯离子通道在组织中分布广泛并参与众多生理功能,其分子基础为跨膜蛋白16A(transmembrane protein 16A,TMEM16A)。近年来研究发现,TMEM16A的表达通过转录、表观遗传和microRNA进行调控,同时研究发现TMEM16A在多种肿瘤细胞中过表达...钙激活氯离子通道在组织中分布广泛并参与众多生理功能,其分子基础为跨膜蛋白16A(transmembrane protein 16A,TMEM16A)。近年来研究发现,TMEM16A的表达通过转录、表观遗传和microRNA进行调控,同时研究发现TMEM16A在多种肿瘤细胞中过表达,并且对不同肿瘤细胞增殖和迁移的影响不同。该文综述了TMEM16A在肿瘤细胞中表达的调控机制及其对肿瘤细胞增殖和迁移的影响,并展望了TMEM16A作为肿瘤标志物的潜在临床应用价值。展开更多
跨膜蛋白16A(transmembrane protein 16A,TMEM16A)作为一种Ca^(2+)激活Cl^(-)通道,在许多恶性肿瘤中高表达。位于染色体11q13区域的TMEM16A基因扩增是导致其过表达的主要原因之一。另外,转录调控、表观遗传调控及microRNAs(miRNAs)在许...跨膜蛋白16A(transmembrane protein 16A,TMEM16A)作为一种Ca^(2+)激活Cl^(-)通道,在许多恶性肿瘤中高表达。位于染色体11q13区域的TMEM16A基因扩增是导致其过表达的主要原因之一。另外,转录调控、表观遗传调控及microRNAs(miRNAs)在许多肿瘤细胞中促进TMEM16A的表达。TMEM16A不仅激活多种促进肿瘤细胞增殖、迁移及侵袭的信号通路,还在抑制肿瘤细胞凋亡方面发挥了重要作用。因此,靶向TMEM16A的抗肿瘤药物研发具有重要的临床意义。本文综述了TMEM16A在恶性肿瘤中的作用机制,深入总结了TMEM16A促进肿瘤发生发展的信号通路,并分析了TMEM16A作为潜在生物标志物在肿瘤发生发展中的关键作用。TMEM16A抑制剂可能成为治疗高表达TMEM16A肿瘤的新方案。展开更多
BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact ...BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact on the associated microenvir-onment consisting of vascular endothelial cells.AIM To explore the role in CRC and the impact on the associated microenvironment consisting of vascular endothelial cells.METHODS Hypoxic conditions prompted examination of SLC16A8 expression,glycolysis,lactate efflux,and Warburg effect correlations in CRC cell lines.Co-culture with HUVEC allowed for endothelial-mesenchymal transition(EndMT)character-ization,revealing lactate efflux's influence.Knockdown of SLC16A8 in CRC cells enabled relevant phenotype tests and tumorigenesis experiments,investigating tumor growth,blood vessel distribution,and signaling pathway alterations.RESULTS SLC16A8 expression was significantly upregulated in CRC tissues compared to adjacent normal tissues and correlated with disease progression(P<0.05).Under hypoxic conditions,HIF-1αinduced SLC16A8 expression,leading to enhanced metabolic reprogramming and increased lactate production.siRNA-mediated SLC16A8 knockdown effectively reversed hypoxia-induced changes,including reduced glucose consumption and lactate production.Co-culture experiments revealed that SLC16A8 knockdown significantly inhibited hypoxia-induced EndMT in HUVEC cells.In vivo studies demonstrated that SLC16A8 knockdown suppressed tumor growth,reduced Ki67 expression,and decreased HIF-1αlevels.Furthermore,SLC16A8 silencing led to decreased ex-pression of key metabolic enzymes PKM2 and LDHA,indicating its role in glycolytic regulation.CONCLUSION Our findings reveal that SLC16A8 functions as a critical mediator of hypoxia-induced metabolic reprogramming in CRC progression.展开更多
文摘钙激活氯离子通道在组织中分布广泛并参与众多生理功能,其分子基础为跨膜蛋白16A(transmembrane protein 16A,TMEM16A)。近年来研究发现,TMEM16A的表达通过转录、表观遗传和microRNA进行调控,同时研究发现TMEM16A在多种肿瘤细胞中过表达,并且对不同肿瘤细胞增殖和迁移的影响不同。该文综述了TMEM16A在肿瘤细胞中表达的调控机制及其对肿瘤细胞增殖和迁移的影响,并展望了TMEM16A作为肿瘤标志物的潜在临床应用价值。
文摘跨膜蛋白16A(transmembrane protein 16A,TMEM16A)作为一种Ca^(2+)激活Cl^(-)通道,在许多恶性肿瘤中高表达。位于染色体11q13区域的TMEM16A基因扩增是导致其过表达的主要原因之一。另外,转录调控、表观遗传调控及microRNAs(miRNAs)在许多肿瘤细胞中促进TMEM16A的表达。TMEM16A不仅激活多种促进肿瘤细胞增殖、迁移及侵袭的信号通路,还在抑制肿瘤细胞凋亡方面发挥了重要作用。因此,靶向TMEM16A的抗肿瘤药物研发具有重要的临床意义。本文综述了TMEM16A在恶性肿瘤中的作用机制,深入总结了TMEM16A促进肿瘤发生发展的信号通路,并分析了TMEM16A作为潜在生物标志物在肿瘤发生发展中的关键作用。TMEM16A抑制剂可能成为治疗高表达TMEM16A肿瘤的新方案。
文摘目的 探究新生儿早发型败血症(EONS)患者血清miR-16a,miR-15b水平表达与临床诊断及预后评估价值研究。方法 选取2020年10月~2023年10月首都医科大学附属北京儿童医院保定医院新生儿科收治的114例确诊为EONS患儿为EONS组,同期选择在该院体检健康的新生儿114例为对照组。对所有EONS患儿进行为期6个月的随访,其中预后不良组34例和预后良好组80例。入院当日6h内采取血清使用实时荧光定量PCR(qRT-PCR)检测miR-16a,miR-15b相对表达水平。受试者工作特征(ROC)曲线分析血清miR-16a,miR-15b对EONS的诊断以及预后评估价值。多因素Logistic回归分析影响EONS预后不良的因素。结果 与对照组相比,EONS组患儿出生时体质量(3.44±0.35kg/m^(2)vs 3.89±0.40kg/m^(2))显著降低,病理学黄疸(35/114 vs 1/114)发生率升高,差异具有统计学意义(t=9.040,χ2=35.922,均P<0.05)。与对照组相比,EONS组患儿血清miR-16a(1.15±0.16 vs 1.01±0.11),miR-15b(1.18±0.15 vs 1.02±0.13)水平显著升高,差异具有统计学意义(t=7.699,8.606,均P<0.05)。血清miR-16a,miR-15b联合诊断EONS的ROC曲线下面积(AUC)高于miR-16a,mi R-15b单独诊断,差异具有统计学意义(Z=2.619,2.157,均P<0.05)。与预后良好组相比,预后不良组出生时体质量显著降低,血清miR-16a,miR-15b水平显著升高,差异具有统计学意义(t=6.724,5.434,6.308,均P<0.05)。血清miR-16a,miR-15b二者联合对EONS预后评估的AUC高于miR-16a,miR-15b单独评估,差异具有统计学意义(Z=2.364,2.073,均P<0.05)。出生时体质量、miR-16a,miR-15b表达水平是EONS预后不良的影响因素(Wald χ^(2)=33.459,16.146,49.797,均P<0.05)。结论 EONS患儿血清中miR-16a,miR-15b呈高表达,二者对EONS有一定的诊断及预后评估价值。
基金Supported by Nanchong Science and Technology Plan Project,No.23JCYJPT0064Project of Sichuan Provincial Administration of Traditional Chinese Medicine,No.2024MS590。
文摘BACKGROUND SLC16A8,a lactate efflux transporter,is upregulated in various cancers,but its effects on tumor microenvironments remain understudied.This research explores its role in colorectal cancer(CRC)and the impact on the associated microenvir-onment consisting of vascular endothelial cells.AIM To explore the role in CRC and the impact on the associated microenvironment consisting of vascular endothelial cells.METHODS Hypoxic conditions prompted examination of SLC16A8 expression,glycolysis,lactate efflux,and Warburg effect correlations in CRC cell lines.Co-culture with HUVEC allowed for endothelial-mesenchymal transition(EndMT)character-ization,revealing lactate efflux's influence.Knockdown of SLC16A8 in CRC cells enabled relevant phenotype tests and tumorigenesis experiments,investigating tumor growth,blood vessel distribution,and signaling pathway alterations.RESULTS SLC16A8 expression was significantly upregulated in CRC tissues compared to adjacent normal tissues and correlated with disease progression(P<0.05).Under hypoxic conditions,HIF-1αinduced SLC16A8 expression,leading to enhanced metabolic reprogramming and increased lactate production.siRNA-mediated SLC16A8 knockdown effectively reversed hypoxia-induced changes,including reduced glucose consumption and lactate production.Co-culture experiments revealed that SLC16A8 knockdown significantly inhibited hypoxia-induced EndMT in HUVEC cells.In vivo studies demonstrated that SLC16A8 knockdown suppressed tumor growth,reduced Ki67 expression,and decreased HIF-1αlevels.Furthermore,SLC16A8 silencing led to decreased ex-pression of key metabolic enzymes PKM2 and LDHA,indicating its role in glycolytic regulation.CONCLUSION Our findings reveal that SLC16A8 functions as a critical mediator of hypoxia-induced metabolic reprogramming in CRC progression.
