肝细胞癌组织miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路和预后的关系研究

摘要 目的：探讨肝细胞癌组织中微小核糖核酸（miR）-124-3p、miR-212-5p表达与磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）信号通路和预后的关系。方法：选择2017年9月至2019年9月徐州医科大学附属医院肝胆外科收治的93例肝细胞癌患者,采用实时荧光定量聚合酶链反应（qRT-PCR）检测肝细胞癌组织中miR-124-3p、miR-212-5p、PI3K 信使RNA（mRNA）、Akt mRNA的表达。Pearson相关性分析miR-124-3p、miR-212-5p表达与PI3K/Akt信号通路相关mRNA表达的相关性。绘制Kaplan-Meier生存曲线,Log-Rank检验不同miR-124-3p、miR-212-5p表达肝细胞癌患者3年总生存率（OS）的差异。结果：肝细胞癌组织中miR-124-3p表达低于癌旁组织（P＜0.05）,miR-212-5p、PI3K mRNA、Akt mRNA表达高于癌旁组织（P＜0.05）。肝细胞癌组织中miR-124-3p表达与PI3K mRNA、Akt mRNA表达呈负相关（P＜0.05）,miR-212-5p表达与PI3K mRNA、Akt mRNA表达呈正相关（P＜0.05）。Ⅱa期、低分化患者肝细胞癌组织中miR-124-3p表达低于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）,miR-212-5p表达高于Ⅰa-Ⅰb期、中高分化患者（P＜0.05）。随访期间死亡37例, miR-124-3p低表达组3年OS为42.55%,低于miR-124-3p高表达组的78.26%（P＜0.05）,miR-212-5p高表达组3年OS为50.00%,低于miR-212-5p低表达组的71.11%（P＜0.05）。结论：肝细胞癌组织中miR-124-3p表达下调,miR-212-5p表达上调,且与肝细胞癌PI3K/Akt信号通路激活,PI3K mRNA和Akt mRNA高表达,低分化,CNLC分期Ⅱa期以及低OS有关。     

喉鳞状细胞癌组织miR-1207-5p、miR-186-5p表达水平与PI3K/Akt信号通路、临床病理特征和预后的关系

摘要 目的：探讨喉鳞状细胞癌（LSCC）组织miR-1207-5p、miR-186-5p表达水平与磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路、临床病理特征和预后的关系。方法：选取2017年1月至2020年1月南充市中心医院收治的120例LSCC患者,取手术切除的LSCC组织和癌旁组织。检测miR-1207-5p、miR-186-5p、PI3K mRNA、Akt mRNA表达。患者出院后随访3年,统计总生存（OS）和无复发生存（RFS）情况。分析miR-1207-5p、miR-186-5p与PI3K、Akt的相关性以及影响LSCC患者预后的因素。结果：LSCC组织miR-1207-5p、miR-186-5p表达低于癌旁组织（P＜0.05）,PI3K mRNA、Akt mRNA表达高于癌旁组织（P＜0.05）。LSCC组织miR-1207-5p、miR-186-5p表达与PI3K mRNA、Akt mRNA表达呈负相关（P＜0.05）。肿瘤直径≥1 cm、低分化、TNM分期Ⅲ期、颈部淋巴结转移LSCC组织中miR-1207-5p、miR-186-5p表达低于肿瘤直径＜1 cm、中高分化、TNM分期Ⅰ～Ⅱ期、无颈部淋巴结转移（P＜0.05）。miR-1207-5p低表达、miR-186-5p低表达LSCC患者3年总生存（OS）率和无复发生存（RFS）率低于miR-1207-5p高表达、miR-186-5p高表达LSCC患者（P＜0.05）。多因素COX回归分析显示TNM III期、颈部淋巴结转移是LSCC患者复发和死亡的危险因素（P＜0.05）,高miR-1207-5p、高miR-186-5p是保护因素（P＜0.05）。结论：LSCC组织中miR-1207-5p和miR-186-5p表达均下调,与LSCC恶性病理特征、PI3K/Akt信号通路激活以及低生存率有关。     

鼻咽癌组织miR-20b-5p、miR-325-3p表达水平与放疗敏感性和预后的关系研究

摘要 目的：探讨鼻咽癌组织微小核糖核酸（miR）-20b-5p、miR-325-3p表达水平与放射治疗敏感性和预后的关系。方法：选取2017年11月至2019年6月我院收治的84例确诊为鼻咽癌并拟进行放射治疗的患者设为鼻咽癌组,另选取同期收治的42例慢性鼻咽炎患者为对照组,比较鼻咽癌组织及鼻咽部炎症组织中miR-20b-5p、miR-325-3p表达水平,分析鼻咽癌组织中miR-20b-5p、miR-325-3p表达水平与鼻咽癌患者临床病理特征的关系。根据鼻咽癌患者放疗敏感性评估结果分为敏感组和抵抗组,比较两组miR-20b-5p、miR-325-3p表达水平。随访3年,Kaplan-Meier法及Cox回归分析法分析miR-20b-5p、miR-325-3p表达水平与鼻咽癌患者生存预后的关系。结果：鼻咽癌组miR-20b-5p、miR-325-3p表达水平均高于对照组（P＜0.05）。不同T分期、N分期、临床分期患者在miR-20b-5p、miR-325-3p高表达组与低表达组中的占比比较存在统计学差异（P＜0.05）。完成7~8周放疗后3个月评估患者放疗抵抗率36.90%,抵抗组miR-20b-5p、miR-325-3p表达水平均高于敏感组（P＜0.05）。miR-20b-5p高表达鼻咽癌患者的累积生存时间短于miR-20b-5p低表达患者（P＜0.05）;miR-325-3p高表达鼻咽癌患者的累积生存时间短于miR-325-3p低表达患者（P＜0.05）。单因素、多因素Cox回归分析显示,年龄＞60岁、T3/T4期、miR-20b-5p高表达、miR-325-3p高表达是鼻咽癌患者预后不良的独立危险因素（P＜0.05）。结论：鼻咽癌组织中miR-20b-5p、miR-325-3p均异常高表达,其表达水平与肿瘤浸润深度、淋巴结转移、临床分期及放疗敏感性有关,且miR-20b-5p、miR-325-3p高表达患者放疗后预后不良风险更大。     

miR-145、miR-186表达与非小细胞肺癌组织临床病理特征和PI3K/Akt/ mTOR信号通路的关系

摘要 目的：探讨微小核糖核酸（miR）-145、miR-186表达与非小细胞肺癌（NSCLC）临床病理特征和磷脂酰肌醇3-激酶（PI3K）/蛋白激酶B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的关系。方法：选择2020年3月至2023年3月我院收治的128例行肺癌根治手术治疗的NSCLC患者,取其术中癌组织和癌旁组织（距离癌组织5 cm以上）,采用实时荧光定量聚合酶链式反应（qRT-PCR）检测miR-145、miR-186以及PI3K mRNA、Akt mRNA、mTOR mRNA表达。分析miR-145、miR-186表达与NSCLC患者临床病理特征的关系;Pearson检验分析NSCLC患者癌组织miR-145、miR-186表达与PI3K mRNA、Akt mRNA、mTOR mRNA表达的相关性。结果：癌组织miR-145、miR-186表达低于癌旁组织（P＜0.05）,低分化、TNM ⅢA期、淋巴结转移的NSCLC组织miR-145、miR-186表达低于中高分化、TNM Ⅰ～Ⅱ期、未发生淋巴结转移的NSCLC组织（P＜0.05）。癌组织PI3K mRNA、Akt mRNA 、mTOR mRNA表达均高于癌旁组织（P＜0.05）,癌组织miR-145、miR-186表达与PI3K mRNA、Akt mRNA、mTOR mRNA表达均呈负相关（P＜0.05）。结论：NSCLC组织中miR-145、miR-186表达下调,miR-145、miR-186表达下调可能激活PI3K/ Akt/mTOR信号通路促使NSCLC进展,且与NSCLC患者癌组织低分化、TNM ⅢA期、淋巴结转移有关。     

血清miR-203a、miR-31-5p、miR-19b-1-5p水平与股骨颈骨折患者骨折延迟愈合的关系及其预测价值分析

摘要 目的：探讨血清微小核糖核酸（miR）-203a、miR-31-5p、miR-19b-1-5p水平与股骨颈骨折患者术后骨折延迟愈合的关系及对术后骨折延迟愈合的预测价值。方法：选择2020年1月~2022年10月在徐州医科大学附属医院行内固定治疗的292例新鲜股骨颈骨折患者为研究对象。于术后4周复查时,检测患者血清miR-203a、miR-31-5p、miR-19b-1-5p水平;并根据其骨折愈合情况分为延迟组（n=36）和愈合组（n=256）。采用多因素Logistic回归分析股骨颈骨折患者术后骨折延迟愈合的影响因素。采用受试者工作特征（ROC）曲线分析血清miR-203a、miR-31-5p、miR-19b-1-5p对股骨颈骨折患者术后骨折延迟愈合的预测价值。结果：术后4个月复查时,骨折延迟愈合发生率为12.33%。两组年龄、吸烟史、合并糖尿病组间比较,差异有统计学意义（P＜0.05）。愈合组血清miR-203a、miR-31-5p、miR-19b-1-5p水平均高于延迟组（P<0.05）。多因素Logistic回归分析结果显示,年龄≥60岁、合并糖尿病、血清miR-203a、miR-31-5p、miR-19b-1-5p水平降低是股骨颈骨折患者术后骨折延迟愈合的独立危险因素（P＜0.05）。ROC曲线结果显示,三者联合检测的曲线下面积（AUC）（0.95CI）为0.841（0.738~0.936）,高于各指标单独应用时的AUC,三者联合检测的灵敏度和特异度亦高于单一指标检测。结论：血清miR-203a、miR-31-5p、miR-19b-1-5p在股骨颈骨折术后骨折延迟愈合患者中呈低表达,是骨折延迟愈合的独立危险因素,三者联合检测对股骨颈骨折患者骨折延迟愈合具有较高的预测价值。     

miR-324-5p、miR-605-3p在脑胶质瘤组织的表达及与临床病理参数和预后的关系

摘要 目的：探讨微小核糖核酸（miRNA）-324-5p、miR-605-3p在脑胶质瘤组织的表达及与临床病理参数和预后的关系。方法：选取2018年1月～2019年12月徐州医科大学附属医院收治的90例脑胶质瘤患者。收集术中部分瘤组织和瘤旁组织,采用实时荧光定量聚合酶链式反应（qRT-PCR）检测miR-324-5p、miR-605-3p表达。根据脑胶质瘤组织中miR-324-5p、miR-605-3p表达的平均值分为高表达组和低表达组,采用Kaplan-Meier法分析不同miR-324-5p、miR-605-3p表达脑胶质瘤患者生存情况,采用多因素Cox回归分析脑胶质瘤患者预后的影响因素。结果：与瘤旁组织比较,脑胶质瘤组织中miR-324-5p、miR-605-3p表达降低（P＜0.05）。不同分化程度、淋巴结转移、世界卫生组织（WHO）中枢神经系统肿瘤分类的脑胶质瘤患者miR-324-5p、miR-605-3p表达比较有差异（P＜0.05）。90例脑胶质瘤患者3年总生存率为36.67%（33/90）。Kaplan-Meier生存曲线分析显示,miR-324-5p高表达组、miR-605-3p高表达组总生存率高于miR-324-5p低表达组、miR-605-3p低表达组（P＜0.05）。多因素Cox回归分析显示,低分化、淋巴结转移和WHO中枢神经系统肿瘤分类Ⅲ～Ⅳ级为脑胶质瘤患者死亡的独立危险因素,miR-324-5p和miR-605-3p升高为独立保护因素（P＜0.05）。结论：脑胶质瘤组织中miR-324-5p、miR-605-3p呈低表达,与分化程度、淋巴结转移、WHO中枢神经系统肿瘤分类有关,miR-324-5p、miR-605-3p低表达还可导致不良预后。     

血清miR-34b-5p、miR-155表达与早产儿急性呼吸窘迫综合征炎症因子和预后的关系分析

摘要 目的：探讨血清微小核糖核酸（miR）-34b-5p、miR-155表达与早产儿急性呼吸窘迫综合征（ARDS）炎症因子和预后的关系。方法：选择2019年2月至2021年3月我院收治的92例ARDS早产儿,根据ARDS病情严重程度将其分为轻度组（31例）、中度组（43例）和重度组（18例）,追踪患儿临床结局,根据院内死亡情况将其分为存活组（51例）和死亡组（41例）。检测所有患儿的血清miR-34b-5p、miR-155表达水平以及白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）水平,比较各组间上述指标差异,分析ARDS早产儿血清miR-34b-5p、miR-155表达与炎症因子的相关性以及miR-34b-5p、miR-155预测ARDS早产儿预后的价值。结果：重度组miR-155表达水平及IL-1β、TNF-α、IL-6水平均高于中度组和轻度组,且中度组高于轻度组（P＜0.05）,重度组miR-34b-5p表达水平低于中度组和轻度组,且中度组低于轻度组（P＜0.05）。死亡组miR-155表达水平及IL-1β、TNF-α、IL-6水平高于存活组（P＜0.05）,死亡组miR-34b-5p表达水平低于存活组（P＜0.05）。ARDS早产儿miR-155表达水平与IL-1β、TNF-α、IL-6水平均呈正相关,而miR-34b-5p表达水平与IL-1β、TNF-α、IL-6水平均呈负相关（P＜0.05）。联合miR-34b-5p、miR-155预测ARDS早产儿死亡的曲线下面积（AUC）为0.853,高于两指标单独预测的0.688、0.649。结论：ARDS早产儿血清miR-34b-5p、miR-155表达水平与患儿血清炎症因子水平以及预后有关,可作为ARDS早产儿病情评估以及预后预测的潜在指标。     

慢性牙周炎患者血清miR-205-5p、miR-28-5p的表达与诊断价值研究

摘要 目的：探讨慢性牙周炎（CP）患者血清微小核糖核酸（miRNA）-205-5p、miR-28-5p表达与牙周指标、炎症反应的关系及诊断价值。方法：选取2021年1月～2022年12月我院口腔科收治的102例CP患者为CP组,根据病情严重程度分为轻度组31例、中度组37例、重度组34例,另选取同期我院65名体检健康者为对照组。采用实时荧光定量聚合酶链式反应（PCR）检测血清miR-205-5p、miR-28-5p表达,酶联免疫吸附法检测白细胞介素（IL）-1β、IL-6、肿瘤坏死因子-α（TNF-α）水平,检查各组牙周指标[菌斑指数（PLI）、牙龈出血指数（BI）、附着丧失（AL）、探诊深度（PD）]。CP患者血清miR-205-5p、miR-28-5p表达与牙周指标和炎症指标的相关性采用Pearson相关性分析。受试者工作特征（ROC）曲线分析血清miR-205-5p、miR-28-5p表达诊断CP的价值。结果：与对照组比较,CP组血清miR-205-5p、miR-28-5p表达降低,PLI、BI、AL、PD和IL-1β、IL-6、TNF-α水平升高（P＜0.05）。轻度组、中度组、重度组血清miR-205-5p、miR-28-5p表达依次降低,PLI、BI、AL、PD和IL-1β、IL-6、TNF-α水平依次升高（P＜0.05）。Pearson相关性分析显示,CP患者血清miR-205-5p、miR-28-5p表达与PLI、BI、AL、PD、IL-1β、IL-6、TNF-α呈负相关（P＜0.05）。ROC曲线分析显示,血清miR-205-5p联合miR-28-5p诊断CP的曲线下面积分别为0.885大于miR-205-5p、miR-28-5p单独检测的0.792、0.790。结论：CP患者血清miR-205-5p、miR-28-5p低表达,与牙周指标、炎症反应密切相关,血清miR-205-5p、miR-28-5p的表达情况可能成为CP辅助诊断指标,且miR-205-5p联合miR-28-5p诊断CP的价值较高。     

支气管哮喘患者血清miR-29a-3p、miR-98-5p表达水平与肺功能、气道炎症和糖皮质激素治疗敏感性的关系研究

摘要 目的：探讨支气管哮喘（BA）患者血清微小核糖核酸（miR）-29a-3p、miR-98-5p表达水平与肺功能、气道炎症和糖皮质激素（GC）治疗敏感性的关系。方法：选取2020年1月～2022年1月潍坊市人民医院收治的150例BA患者为BA组,根据BA患者GC治疗敏感性将其分为抵抗组43例和敏感组107例,另选取同期57名体检健康者为对照组。收集BA组、对照组肺功能和气道炎症指标资料,采用实时荧光定量逆转录聚合酶链式反应（qRT-PCR）检测两组血清miR-29a-3p、miR-98-5p表达水平。通过Spearman相关性分析BA患者血清miR-29a-3p、miR-98-5p表达水平与肺功能和气道炎症指标的相关性,单因素和多因素Logistic回归分析BA患者GC治疗抵抗的影响因素。结果：与对照组比较,BA组血清miR-29a-3p、miR-98-5p表达水平和第1秒用力呼气容积占预计值百分比（FEV₁％）、第1秒用力呼气容积/用力肺活量（FEV₁/FVC）、峰值呼气流速（PEF）降低,呼出气一氧化氮（FeNO）水平升高（P均＜0.05）。Spearman相关性分析显示,BA患者血清miR-29a-3p、miR-98-5p表达水平与FEV₁％、FEV₁/FVC、PEF呈正相关,与FeNO水平呈负相关（P均＜0.05）。单因素分析显示,抵抗组体质指数＞24 kg/m²、吸烟比例高于敏感组,血清miR-29a-3p、miR-98-5p表达水平低于敏感组（P＜0.05）。多因素Logistic回归分析显示,体质指数＞24 kg/m²、吸烟为BA患者GC治疗抵抗的独立危险因素,血清miR-29a-3p、miR-98-5p表达水平升高为其独立保护因素（P均＜0.05）。结论：BA患者血清miR-29a-3p、miR-98-5p水平降低,与肺功能下降、气道炎症和GC治疗抵抗有关。     

下调lncRNA MCF2L-AS1靶向miR-33b-5p抑制胃癌细胞增殖、迁移、侵袭并促进凋亡

摘要 目的：探讨lncRNA MCF2L-AS1对胃癌细胞恶性生物学行为的影响及分子机制。方法：选取45例胃癌患者的癌组织及癌旁正常组织,或培养胃黏膜上皮细胞GES-1、胃癌细胞HGC-27,采用RT-qPCR检测MCF2L-AS1和miR-33b-5p的表达水平。采用双荧光素酶报告实验检测MCF2L-AS1和miR-33b-5p的靶向关系。将HGC-27细胞分为si-NC组、si-MCF2L-AS1组、mimic NC组、miR-33b-5p mimic组、si-MCF2L-AS1+inhibitor NC组、si-MCF2L-AS1+miR-33b-5p inhibitor组,分别转染si-NC、si-MCF2L-AS1、mimic NC、miR-33b-5p mimic或共转染si-MCF2L-AS1+inhibitor NC、si-MCF2L-AS1+miR-33b-5p inhibitor。采用MTT实验检测细胞增殖情况,流式细胞术检测细胞凋亡率,克隆形成实验检测细胞克隆形成数,Transwell实验检测迁移和侵袭细胞数。结果：与癌旁正常组织或GES-1细胞相比,胃癌组织或HGC-27细胞中MCF2L-AS1表达水平升高、miR-33b-5p表达水平降低,差异均有统计学意义（P<0.05）。MCF2L-AS1可靶向调控miR-33b-5p。下调MCF2L-AS1或过表达miR-33b-5p,miR-33b-5p表达水平升高,HGC-27细胞凋亡率升高,但细胞增殖、克隆形成数、迁移和侵袭数均减少,差异均有统计学意义（P<0.05）。抑制miR-33b-5p可减弱下调MCF2L-AS1对HGC-27细胞的生物学作用。结论：下调MCF2L-AS1通过上调miR-33b-5p抑制胃癌细胞增殖、迁移、侵袭并促进凋亡;MCF2L-AS1通过靶向调控miR-33b-5p表达进而参与胃癌细胞的恶性生物学行为。     

miR-15a-5p和miR-16-5p在骨肉瘤组织中的表达分析

目的:使用microRNAs基因芯片及实时定量PCR法测定骨肉瘤组织中miR-15a-5p和miR-16-5p的相对表达含量,并与瘤旁组织对比,分析骨肉瘤细胞内miR-15a-5p和miR-16-5p的表达变化。方法:选取34例骨肉瘤组织蜡块样本,使用microRNAs基因芯片观察miR-15a-5p和miR-16-5p在骨肉瘤和瘤旁组织内的表达差异;实时定量PCR法测定骨肉瘤组织和瘤旁组织中miR-15a-5p和miR-16-5p的相对表达含量,并将两种结果对比分析。结果:microRNAs基因芯片结果显示,在骨肉瘤组织中,miR-15a-5p在肿瘤中的表达较瘤旁组织低1.79倍,miR-16-5p较瘤旁组织低1.62倍。实时定量PCR实验结果表明,miR-15a-5p和miR-16-5p表达较瘤旁组织降低,差异有统计学意义(P0.05)。经过统计学计算,miR-15a-5p在肿瘤中的表达较瘤旁组织低3.14倍,miR-16-5p较瘤旁组织低5.65倍。结论:在骨肉瘤中,miR-15a-5p和miR-16-5p表达含量降低,提示这两种microRNAs在骨肉瘤中可能做为抑癌因子存在。     

Circulating miR-3613-5p but not miR-125b-5p,miR-199a-3p,and miR-451a are biomarkers of endometriosis

ObjectiveThis study aimed to assess the utility of circulating miR-125b-5p, miR-199a-3p, miR-451a, and miR-3613-5p as biomarkers of endometriosis.Study designPatients with stage III or IV of endometriosis according to the revised American Society of Reproductive Medicine (rASRM) staging classification, as well as control women, were recruited. We created a prospective study conducted on a group of 48 patients (n = 25 controls, n = 24 endometriosis) who had laparoscopic surgery. Blood samples were taken and plasma miRNA levels were measured by quantitative real-time polymerase chain reaction (RT-qPCR) and assessed with AUC and ROC curves.ResultsMiR-451a and miR-3613-5p were significantly decreased in the plasma of endometriosis patients. miR-451a had a receiver-operating characteristic (ROC) area under the curve 0.8283 and miR-3613-5p had a ROC area under the curve 0.7617. The concentration of circulating miR-125b-5p and miR-199-3p did not differ between endometriosis patients and controls. Plasma miRNA levels did not change with BMI, smoking status, fertility problems, or menstrual pain according to the VAS scale (p > 0.05).ConclusionCirculating miR-451a and miR-3613-5p levels significantly differed between endometriosis and controls. However, the levels of miR-451a were discordant with previous studies. Therefore, miR-3613-5p may have better potential as the endometriosis biomarker. Circulating miR-125b-5p and miR-199a-3p cannot be used as reliable markers of endometriosis.     

miR-181a/b-5p regulates human umbilical vein endothelial cell angiogenesis by targeting PDGFRA

Type 2 diabetes mellitus (T2DM) is a growing burden in low-and middle-income countries. Changing lifestyles and lack of physical activity are some of the reasons contributing to this epidemic increase. Co-morbidities associated with T2DM are largely due to the complications which arise as a consequence of endothelial dysfunction. Platelet derived growth factor-alpha (PDGFRA) is a protein responsible for cell proliferation, angiogenesis, migration and invasion. Increased levels of PDGFRA have been reported in T2DM. This study assessed the epigenetic regulation of PDGFRA through microRNAs (miR-181a/b-5p).Using a bioinformatics-based approach, we assessed the binding of miR-181a/b-5p to PDGFRA. Experimentally, this binding was confirmed using a dual luciferase reporter assay. Further, we overexpressed miR-181a/b-5p in Human umbilical vein endothelial cells (HUVECs) and the influence of over-expression on cell proliferation, migration and angiogenesis was assessed using in-vitro approaches. The influence of miR-181a/b-5p over expression on cellular apoptosis was ascertained using a TUNEL assay with concomitant changes being observed in the levels of Bcl-2 and cleaved Caspase-3.In HUVECs, PDGFRA is a direct target for miR-181a/b-5p. Over expression of miR-181a/b-5p decreased cellular proliferation, migration, invasion, and tube formation—a surrogate marker for angiogenesis. miR-181a/b-5p may be used as a therapeutic intervention to restrict uncontrolled levels of PDGFRA and thereby rescue the phenotypes of increased cell proliferation, migration, invasion and tube formation. miR-181a/b negatively regulates PDGFRA levels. Significance of the study : T2DM and its associated complications emerge from endothelial dysfunction. The associated phenotypes are regulated by a number of proteins, one such member being, PDGFRA. PDGFRA is in turn regulated by miR-181a/b-5p. Complementation with miR-181a/b-5p resulted in reversion of phenotypes. Thus, miR-181a/b-5p-mediated suppression of PDGFRA may be used as a therapeutic intervention in the management of type 2 diabetes.     

Sevoflurane protects cardiomyocytes against hypoxia/reperfusion injury via LINC01133/miR-30a-5p axis

Previous studies failed to elucidate the detailed mechanisms of anesthetic preconditioning as a protective approach against ischemic/reperfusion (I/R) injury in cells. The present study mainly centered on discovering the mechanisms of Sevoflurane (Sev) in preventing cardiomyocytes against I/R injury. Human cardiomyocyte AC16 cell line was used to simulate I/R injury based on a hypoxia/reperfusion (H/R) model. After Sev treatment, cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Lactate dehydrogenase (LDH) content was measured using an LDH Detection Kit. Relative mRNA and protein expressions of LINC01133, miR-30a-5p and apoptosis-related proteins were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot as needed. Target gene of miR-30a-5p and their potential binding sites were predicted using Starbase and confirmed by dual-luciferase reporter assay. Cell behaviors were assessed again after miR-30a-5p and LINC01133 transfection. Sev could improve cell viability, reduce LDH leakage, and down-regulate the expressions of apoptosis-related proteins (Bax, cleaved caspase-3 and cleaved caspase-9) and LINC01133 as well as up-regulate miR-30a-5p and Bcl-2 expressions in H/R cells. MiR-30a-5p was the target of LINC01133, and up-regulating miR-30a-5p enhanced the effects of Sev in H/R cells, with a suppression on H/R-induced activation of the p53 signaling pathway. However, up-regulating LINC01133 reversed the enhancing effects of miR-30a-5p on Sev pretreatment in H/R cells. Sev could protect cardiomyocytes against H/R injury through the miR-30a-5p/LINC01133 axis, which may provide a possible therapeutic method for curing cardiovascular I/R injury.     

miR-181a/b-5p ameliorates inflammatory response in monocrotaline-induced pulmonary arterial hypertension by targeting endocan

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by vascular remodeling, endothelial cell (EC) dysfunction, and inflammation. The roles of microRNAs have received much critical attention. Thus, this study was attempted to show the biological function of miR-181a/b-5p (miR-181a/b) in monocrotaline (MCT)-induced PAH. Here, rats injected with MCT were used as PAH models. The expression of miR-181a/b and its effect on PAH pathologies were examined using miR-181a/b overexpression lentivirus. A luciferase reporter analysis was performed to measure the relationships between miR-181a/b and endocan. Additionally, primary rat pulmonary arterial endothelial cells (rPAECs) treated with tumor necrosis factor-α (TNF-α) were employed to further validate the regulatory mechanism of miR-181a/b in vitro. Our results showed that miR-181a/b expression was reduced in PAH, and its upregulation significantly attenuated the short survival period, right ventricular systolic pressure and mean pulmonary artery pressure increments, right ventricular remodeling, and lung injury. Furthermore, the increase of intercellular cell adhesion molecule-1 (ICAM1) and vascular cell adhesion molecule-1 (VCAM1) in PAH rats was inhibited by miR-181a/b overexpression. Similarly, our in vitro results showed that inducing miR-181a/b suppressed TNF-α-stimulated increase of ICAM1 and VCAM1 in rPAECs. Importantly, the increased expression of endocan in PAH model or TNF-α-treated rPAECs was restored by miR-181a/b upregulation. Further analysis validated the direct targeting relationships between miR-181a/b and endocan. Collectively, this study suggests that miR-181a/b targets endocan to ameliorate PAH symptoms by inhibiting inflammatory states, shedding new lights on the prevention and treatment of PAH.     

miR-625-5p/PKM2 negatively regulates melanoma glycolysis state

PKM2 plays an important role in cancer glycolysis, however, the link of PKM2 and microRNAs (miRNAs) in melanoma is still unclear. The study will investigate the role of miRNAs in regulating PKM2 mediated melanoma cell glycolysis. We found that high PKM2 expression in melanoma tissues and cell lines was positively associated with glycolysis. Further study indicated that miR-625-5p regulated PKM2 expression on mRNA and protein levels in melanoma cells. There was a negative relationship between miR-625-5p and PKM2 expression in the clinical melanoma samples. These findings provide an evidence that miR-625-5p/PKM2 plays a role in melanoma cell glucose metabolism.