过表达miR-31对结肠炎模型小鼠TLR4/NF-κB信号通路及凋亡蛋白的调控

目的: 探讨miR-31对DSS诱发结肠炎小鼠TLR4/NF-κB信号通路和凋亡相关蛋白的影响。方法: ①小鼠结肠炎实验:用1%葡聚糖硫酸钠(DSS)诱发小鼠溃疡性结肠炎(UC)。14只FVB非转基因小鼠随机分为control组(n=6),DSS组(n=8),16只FVB miR-31转基因小鼠随机分为miR-31过表达组(n=8),miR-31过表达+DSS 组(n=8),DSS溶于水后通过饮水给予小鼠。DSS组和miR-31+DSS组第一周饮用1%DSS水,第二周饮用正常无菌水,第三周饮用1%DSS水,如此5周后造模完成,之后留取小鼠的结肠组织,通过Western blot和IHC检测小鼠结肠组织NF-κB p65、TLR4、Bax、Bcl-2蛋白的表达;TUNEL检测小鼠结肠组织细胞凋亡。②细胞培养实验:在人结肠上皮细胞系HCT 116细胞中通过脂质体转染的方法转染miR-31 mimic和inhibitor,使miR-31过表达或敲低,每组均进行三次重复,48 h后收取细胞,通过Western blot检测NF-κB p65、TLR4蛋白的表达。结果: ①动物实验中,与control组相比,小鼠结肠组织中DSS组和miR-31过表达组NF-κB p65、TLR4蛋白表达水平和凋亡细胞指数均显著升高(P＜0.05或P＜0.01),Bcl-2/Bax比值显著降低(P＜0.05或P＜0.01);且与DSS组相比,miR-31+DSS组NF-κB p65、TLR4蛋白表达水平和凋亡细胞指数也显著升高(P＜0.01),Bcl-2/Bax比值显著降低(P＜0.01)。②细胞实验中,与control组相比, HCT 116细胞过表达miR-31组的NF-κB p65、TLR4蛋白表达水平均显著升高(P＜0.05或P＜0.01),敲低miR-31组的NF-κB p65、TLR4蛋白表达水平下降(P＜0.05)。结论: miR-31通过促进TLR4/NF-κB信号通路和介导肠上皮细胞凋亡促进结肠炎的发展。     

MiR-146a通过炎症参与小鼠糖尿病心肌病的机制研究

目的:探讨microRNA-146a (miR-146a)对小鼠糖尿病心肌病炎症的影响。方法:20只雄性C57BL/6小鼠随机分为对照组和糖尿病心肌模型组,模型组利用链脲佐菌素(STZ,50 mg/kg)腹腔注射建立糖尿病心肌病模型,对照组给予等体积枸橼酸钠缓冲液,建模成功后提取心脏组织RNA,利用qRT-PCR检测心肌组织中miR-146a和炎症因子白介素1β(IL-1β),白介素6(IL-6),单核趋化因子1(MCP-1)以及NF-κB/p65的mRNA表达;依次分离原代心肌细胞,成纤维细胞和内皮细胞,给予高糖处理后,检测细胞中miR-146a,IL-1β,IL-6,MCP-1以及NF-κB/p65的mRNA表达;内皮细胞转染miR-146a mimic或miR-146a inhibitor,观察炎症因子的表达情况。结果:糖尿病心肌病心肌组织中miR-146a水平较对照组降低(P0.05),炎症因子IL-1β,IL-6,MCP-1以及NF-κB/p65的mRNA表达高于对照组(P0.05);与对照组相比,高糖分别处理原代心肌细胞和成纤维细胞后miR-146a表达未改变(P0.05),而高糖降低内皮细胞中miR-146a的表达(P0.05);高糖增加内皮细胞炎症因子IL-1β,IL-6,MCP-1及NF-κB/p65的mRNA水平(P0.05);内皮细胞转染miR-146a mimic后可阻止由于高糖所导致的内皮细胞中IL-1β,IL-6,MCP-1及NF-κB/p65的增加(P0.05),而转染miR-146a inhibitor后,可引起正常对照组细胞中炎症因子IL-1β,IL-6,MCP-1以及NF-κB/p65表达的增加(P0.05)。结论:糖尿病心肌病中miR-146a的降低以及炎症的增加,与内皮细胞受损相关,且可能通过miR-146a影响炎症因子的表达。     

地佐辛对缺氧复氧诱导的大鼠心肌细胞损伤的作用及机制

目的: 探讨地佐辛通过调控微小RNA-7a-5p(miR-7a-5p)/泛素E3连接酶10(TRIM10)表达影响缺氧复氧(H/R)诱导的大鼠心肌细胞H9C2氧化应激和凋亡的作用机制。方法: 将H9C2细胞分为对照组(细胞正常培养)、H/R组(缺氧处理3 h,复氧培养4 h)、不同剂量地佐辛干预组(分别采用10^-7、10^-6、10^-5 mmol/L的地佐辛预处理H9C2细胞24 h,再进行H/R处理)、H/R+miR-7a-5p组(转染miR-7a-5p mimics至H9C2细胞,然后进行H/R处理)、H/R+miR-NC组(转染miR-NC至H9C2细胞,然后进行H/R处理)、H/R+地佐辛+anti-miR-7a-5p组(10^-5 mmol/L的地佐辛预处理转染anti-miR-7a-5p的H9C2细胞24 h,再进行H/R处理)、H/R+地佐辛+anti-miR-NC组(10^-5 mmol/L的地佐辛预处理转染anti-miR-NC的H9C2细胞24 h,再进行H/R处理),每组细胞设置3个复孔,实验重复3次。酶联免疫吸附法检测细胞中氧化应激指标丙二醛(MDA)含量、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活力,流式细胞术检测细胞凋亡,蛋白印迹(Western blot)法检测B淋巴细胞瘤-2(Bcl-2)、B淋巴细胞瘤-2相关蛋白(Bax)和泛素E3连接酶10(TRIM10)蛋白表达,实时荧光定量PCR(RT-qPCR)检测miR-7a-5p和TRIM10 mRNA表达。双荧光素酶报告基因实验验证miR-7a-5p与TRIM10调控关系。结果: 与对照组比较,H/R组MDA含量、细胞凋亡率、Bax蛋白表达及TRIM10的mRNA和蛋白表达均升高(P＜0.05),而SOD和GSH-Px活力、Bcl-2蛋白表达和miR-7a-5p表达均降低(P＜0.05)。与H/R组比较,不同剂量地佐辛干预组MDA含量、细胞凋亡率、Bax蛋白表达及TRIM10的mRNA和蛋白表达均降低(P＜0.05),而SOD和GSH-Px活力、Bcl-2蛋白表达和miR-7a-5p表达均升高(P＜0.05),且不同剂量地佐辛干预组间各指标两两比较差异均显著(P＜0.05)。与H/R+miR-NC组比较,H/R+miR-7a-5p组MDA含量、细胞凋亡率、Bax蛋白表达及TRIM10蛋白表达均降低(P＜0.05),而SOD和GSH-Px活力、Bcl-2蛋白表达均升高(P＜0.05)。miR-7a-5p靶向负调控TRIM10表达。与H/R+地佐辛+anti-miR-NC组比较,H/R+地佐辛+anti-miR-7a-5p组MDA含量、细胞凋亡率、Bax蛋白表达及TRIM10蛋白表达均升高(P＜0.05),而SOD和GSH-Px活力、Bcl-2蛋白表达均降低(P＜0.05)。结论: 地佐辛可降低H/R诱导的大鼠心肌细胞H9C2氧化应激和凋亡,其可能通过调控miR-7a-5p/TRIM10轴发挥作用。     

Apelin-13对LPS诱导人脐静脉内皮细胞屏障损伤的干预作用*

目的: 探讨Apelin-13对LPS诱导人脐静脉内皮细胞(HUVECs)屏障损伤的影响。方法: 将体外培养的HUVECs分为4组:正常对照组、LPS组、Apelin-13+LPS组、Apelin-13组。用5 μg/ml LPS作用细胞24 h, 复制屏障功能受损模型。1 μmol/L Apelin-13提前30 min给予,再给予LPS作用24 h,确定Apelin-13的影响。通过CCK8法检测Apelin-13对细胞活力的影响;Western blot检测血管内皮细胞钙粘蛋白(VE-cadherin)、纤维状肌动蛋白(F-actin)表达变化;免疫荧光检测VE-cadherin、F-actin的表达变化及核转录因子Kappa B(NF-κB p65)入核情况。结果: 与正常对照组相比,单独给予Apelin-13对细胞活力无明显影响。与正常对照组相比,LPS组细胞活力明显下降(P＜0.01),VE-cadherin蛋白表达下降(P＜0.01)、F-actin蛋白表达升高(P＜0.05),NF-κB p65入核明显增加。与LPS组相比,Apelin-13明显增加细胞活力(P＜0.01),VE-cadherin蛋白表达增加(P＜0.05)、F-actin蛋白表达下降(P＜0.01),蛋白NF-κB p65入核下降明显。结论: Apelin-13可减轻LPS诱导的人脐静脉内皮细胞损伤及屏障受损,其机制可能与抑制炎症相关。     

莪术醇对非酒精性脂肪性肝大鼠肝功能和肝纤维化的影响及机制*

目的:探讨莪术醇(CC)对非酒精性脂肪性肝(NAFLD)大鼠模型肝功能和肝纤维化的影响及机制。方法:采用高脂饮食构建非酒精脂肪肝炎(NASH)伴肝纤维化的大鼠模型,将60只SD大鼠随机分为:空白对照组、模型组(NASH)、NASH+复方鳖甲软肝片(CBT)组(阳性对照组)、NASH+CC组(25、50、100 mg/kg),每组10只。测量大鼠肝脏占体重的百分比,测量大鼠高密度脂蛋白(HDL)、甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST)水平,HE染色观察肝纤维化情况,免疫组化检测鼠肝组织α-平滑肌肌动蛋白(α-SMA)表达及肝组织核因子κB p65(NF-κB p65)的阳性染色情况,蛋白印迹(Western blot)检测α-SMA、基质金属蛋白酶-1(MMP-1)、基质金属蛋白酶抑制剂-1(TIMP-1)蛋白表达及Toll样受体-4(TLR4)、转化生长因子激活激酶-1(TAK1)、NF-κB p65、血管细胞粘附分子-1(VCAM-1)蛋白的表达情况,酶联免疫吸附法(ELISA)检测肝组织中白介素(IL-6、IL-10、IL-1β)、肿瘤坏死因子-α(TNF-α)的表达。结果:与空白对照组相比,模型组大鼠HDL、 IL-10含量、MMP-1蛋白表达量显著降低(P＜0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著升高(P＜0.05)。与模型组相比,CBT和CC处理后大鼠HDL、 IL-10含量、MMP-1蛋白表达量显著升高(P＜0.05),TG、ALT、AST、肝组织P65阳性率,α-SMA、TIMP-1、TLR4、TAK1、NF-κB p65、VCAM-1表达、IL-6、TNF-α及IL-1β含量显著降低(P＜0.05),其中模型+CC组以高浓度组改善最显著(P＜0.05),但各剂量改善幅度均低于模型+CBT组(P＜0.05)。结论:莪术醇通过调节TLR4、TAK1、NF-κB p65信号通路,减轻炎症反应,改善肝功能,从而缓解非酒精性脂肪肝肝肝纤维化,且在一定范围内呈浓度依赖性。     

细胞周期蛋白依赖性激酶在miR-193a5p调控卵巢癌细胞增殖及上皮细胞间充质转变中的作用*

目的: 探讨miR-193a-5p靶向CDK14并调控卵巢癌细胞OVAC的增殖和上皮间充质转变(EMT)的作用。方法: 通过TargetScanHuman分析miR-193a-5p与CDK14的匹配情况,通过荧光素酶报告系统检测miR-193a-5p靶向CDK14情况;在miR-193a-5p mimics过表达或者miR-193a-5p inhibitor基因沉默miR-193a-5p的情况下,采用免疫印迹检测CDK14,EMT相关蛋白质E-cadherin、vimentin、fibronectin和N-cadherin的表达量,采用CCK-8检测卵巢癌细胞OVAC增殖情况, MMT检测卵巢癌细胞OVAC的细胞活力。结果: miR-193a-5p靶向CDK14的3‘UTR;过表达miR-193a-5后, CDK14的表达下降,EMT相关蛋白质E-cadherin的表达上升,vimentin、fibronectin和N-cadherin的表达下降,卵巢癌细胞OVAC的增殖和细胞活力均增加;同时,基因沉默miR-193a-5p后, CDK14的表达上升,EMT相关蛋白质E-cadherin的表达下降,vimentin、fibronectin和N-cadherin的表达量上升,卵巢癌细胞OVAC的增殖和细胞活力均减少。结论: miR-193a-5p通过靶向CDK14的3‘UTR降低卵巢癌细胞OVAC的增殖、细胞活力和EMT。     

加味逍遥散对LPS诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响*

目的: 观察加味逍遥散对LPS诱导的抑郁模型大鼠海马小胶质细胞TLR4/NF-κB通路的影响,探讨其抗抑郁机制。方法: 将SD大鼠随机分为对照组、模型组、氟西汀组(10.8 mg·kg^-1)、加味逍遥散低、高剂量组(3.64、7.28 g·kg^-1)。采用慢性LPS注射(ip,0.5 mg·kg^-1)的方法建立抑郁大鼠模型,于造模同时灌胃给药,共14 d。采用旷场和强迫游泳实验评价大鼠的抑郁样行为,免疫组化法检测海马小胶质细胞标志蛋白Iba-1的表达,ELISA法检测海马匀浆液中TNF-α、IL-6的含量,Western blot法检测海马TLR4、NF-κB蛋白的表达。结果: 与对照组比较,模型组大鼠抑郁样行为显著(P＜0.01),海马小胶质细胞明显激活(P＜0.01),TNF-α、IL-6含量增加(P＜0.01),TLR4、NF-κB蛋白明显上调(P＜0.01);与模型组比较,氟西汀和高剂量加味逍遥散组大鼠抑郁样行为明显缓解(P＜ 0.05),小胶质细胞Iba-1表达恢复正常(P＜0.01),TNF-α、IL-6含量下降(P＜0.01),TLR4、NF-κB蛋白表达下调(P＜0.05);与氟西汀组比较,高剂量加味逍遥散组各指标无统计学差异,提示两者抗抑郁功效无显著区别。结论: 加味逍遥散能明显改善大鼠的抑郁样行为,其机制可能与抑制小胶质细胞TLR4/NF-κB通路,进而下调炎症因子的表达有关。     

抗阻运动对胰岛素抵抗小鼠海马内焦亡相关蛋白的影响*

目的: 探讨胰岛素抵抗小鼠海马内焦亡相关蛋白的变化,以及抗阻训练对海马内焦亡相关蛋白的调节作用。方法: 6周龄C57BL/6J雄性小鼠随机分为对照组(C, n=12)和高脂膳食组(HFD, n=26)分别进行普通膳食或高脂膳食喂养12周。随后根据葡萄糖耐量实验(GTT)和胰岛素耐量实验(ITT)的结果,将HFD组分为胰岛素抵抗组(IR, n=10)和抗阻运动组(RT, n=10),维持高脂膳食喂养同时RT组小鼠进行抗阻训练。12周后,全部小鼠麻醉后处死,取脑并剥离出海马组织,通过Western blot检测焦亡相关蛋白的表达。结果: 与C组相比,IR组小鼠海马内NF-κB、NLRP3炎症小体、下游焦亡相关蛋白GSDMD-N和GSDMD以及炎症因子IL-1β和IL-18的蛋白表达量显著性上升(P＜0.05),SIRT1蛋白表达量以及p-AMPK蛋白水平显著性下降(P＜0.05);与IR组相比,RT组小鼠海马内NF-κB、NLRP3炎症小体、下游焦亡相关蛋白GSDMD-N和GSDMD以及炎症因子IL-1β和IL-18的蛋白表达量显著性下降(P＜0.05),SIRT1蛋白表达量以及p-AMPK蛋白水平显著性上升(P＜0.01)。结论: 胰岛素抵抗小鼠海马内NLRP3炎症小体被激活,介导海马内发生细胞焦亡;经过12周的抗阻运动可有效抑制NLRP3炎症小体激活,改善海马内细胞焦亡和炎症状态。     

黄连素对PCOS模型大鼠LPS /NF-κB、MAPK信号通路的影响*

目的: 探讨黄连素对多囊卵巢综合征(PCOS)模型大鼠糖脂代谢、性激素结合蛋白和脂联素(LPS)以及NF-κB、MAPK信号通路的影响。方法: 将SD雌性大鼠随机分成空白组、PCOS模型组、黄连素组(0.216 g/kg)、二甲双胍组(0.135 g/kg)和达英-35(0.18 mg/kg)组,每组10只。PCOS模型组用来曲唑(1 mg/(kg·d))连续灌胃3周,随后药物干预28 d,检测大鼠体重、卵巢和子宫指数,HE染色观察大鼠卵巢卵泡数量变化,用ELISA法检测血清性激素水平、空腹葡萄糖和胰岛素、甘油三酯和胆固醇、性激素结合蛋白和脂联素水平以及用蛋白印迹法检测卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达。结果: 与空白组比较,模型组大鼠体重显著增加(P＜0.05),子宫指数显著降低(P＜0.05),囊状卵泡数量显著增加(P＜0.05),血清黄体生成素(LH)、睾酮(T)水平和LH/FSH比值显著升高(P＜0.05),卵泡刺激素(FSH)水平显著下降(P＜0.05),总胆固醇(TC)、甘油三酯(TG)、空腹胰岛素和胰岛素指数(HOMA)显著增加(P＜0.05),性激素结合蛋白(SHBG)含量显著减少以及脂联素(LPS)含量显著增加(P＜0.05),卵巢组织p38-MAPK、c-Jun和NF-κB蛋白表达上调(P＜0.05)。与模型组比较,黄连素能显著增加子宫指数(P＜0.05)、次级卵泡数量(P＜0.05),显著降低血清促黄体生成素(LH)水平、睾酮(T)水平和LH/FSH比值(P＜ 0.05),显著下调卵巢组织p38-MAPK和NF-κB蛋白表达(P＜0.05),作用类似达英-35;黄连素能明显降低血清甘油三酯(TG)、胰岛素水平和胰岛素指数(P＜0.05),升高血清SHBG水平,降低LPS水平(P＜0.05),作用类似二甲双胍。结论: 黄连素通过下调卵巢组织p38-MAPK和NF-κB蛋白表达,降低血清LPS含量,起到调控PCOS大鼠性激素紊乱和胰岛素抵抗(IR)的作用。     

Mir-335-5p靶向G6PD对结肠癌细胞增殖、凋亡的影响

目的: 探讨Mir-335-5p通过靶向G6PD对结肠癌细胞增殖、凋亡的影响。方法: 设置正常结肠细胞组、空白对照组、NC组、miRNA-335-5p mimic组;体外培养结肠上皮细胞(IEC)和人源性结肠癌细胞SW480,并对NC组、miRNA-335-5p mimic组细胞进行转染;采用RT-qPCR检测各组细胞中miR-335-5p及G6PD mRNA表达水平;双荧光素酶报告实验验证Mir-335-5p对G6PD靶向作用;MTT实验检测各组细胞的增殖;流式细胞术检测转染后各组细胞凋亡率;Western blot检测G6PD及凋亡蛋白Bax、Bcl-2、caspase3相对表达水平。结果: 与正常结肠细胞相比,空白对照组、NC组结肠癌细胞SW480细胞中miR-335-5p相对表达水平降低,G6PD mRNA相对表达水平升高(P＜0.05);与空白对照组、NC组相比,miR-335-5p mimic组细胞miR-335-5p表达水平明显升高,G6PD mRNA表达水平显著降低(P＜0.05)。与空白对照、NC组相比,miR-335-5p mimic组结肠癌SW480细胞生长活性显著降低,凋亡率显著升高(P＜0.05)。miR-335-5p mimic+WT-G6PD 3′-UTR组的荧光素酶相对活性低于miR-335-5p NC+WT-G6PD 3′-UTR组(P＜0.05)。与空白对照组相比,miR-335-5p mimic组细胞中G6PD、Bcl-2蛋白相对表达水平显著降低,Bax、caspase3蛋白表达水平显著升高(P＜0.05)。结论: Mir-335-5p可能通过靶向G6PD抑制结肠癌细胞增殖、促进凋亡。     

RELA/NEAT1/miR-302a-3p/RELA feedback loop modulates pancreatic ductal adenocarcinoma cell proliferation and migration

Pancreatic ductal adenocarcinoma (PDAC) remains a challenging malignancy due to distant metastasis. RELA, a major component of the NF-κB pathway, could serve as an oncogene through activating proliferation or migration-related gene expression, including NEAT1, a well-known oncogenic long noncoding RNA. In the current study, the expression and function of RELA and NEAT1 in PDAC were examined. The potential upstream regulatory microRNAs of RELA were screened and verified for their correlation with RELA and NEAT1. The expression and function of the selected miR-302a-3p were evaluated. RELA and NEAT1 expression were upregulated in PDAC tissues, particularly in PDAC tissues with lymph node metastasis, and their expression correlated with clinical parameters. RELA overexpression promoted PDAC cell proliferation and migration, which could be partially attenuated by the NEAT1 knockdown. By binding to RELA, miR-302a-3p inhibited RELA expression, as well as PDAC cell proliferation and migration. RELA downstream NEAT1 expression was negatively regulated by miR-302a-3p; the suppressive effect of NEAT1 knockdown on PDAC cell proliferation and migration was partially attenuated by miR-302a-3p inhibition. Moreover, through direct binding, the expression of miR-302a-3p was also negatively regulated by NEAT1. The expression of miR-302a-3p was downregulated and negatively correlated with RELA or NEAT1 in tissue samples, indicating that rescuing miR-302a-3p expression may inhibit PDAC cell proliferation and migration through RELA/NEAT1. In summary, RELA, NEAT1, and miR-302a-3p form a feedback loop in PDAC to modulate PDAC cell proliferation and migration.     

miR-382-3p suppressed IL-1β induced inflammatory response of chondrocytes via the TLR4/MyD88/NF-κB signaling pathway by directly targeting CX43

miR-382-3p has been reported to be upregulated in synovial membrane in knee osteoarthritis (OA). Nevertheless, its role in OA remains largely unknown. The aim of this study was to investigate the specific function and mechanisms of miR-382-3p in the course of OA. In this study, human OA chondrocytes were pretreated with interleukin-1β (IL-1β) at 5 ng/ml for 12 hr to stimulate inflammatory response and matrix metalloproteinases (MMPs) expression in chondrocytes. Meanwhile, miR-382-3p was downregulated in IL-1β-stimulated chondrocytes. In addition, we found that miR-382-3p directly interacts with connexin 43 (CX43) and attenuates the increase of cytochrome c oxidase polypeptide II, inducible nitric oxide synthase, and MMP-1/13 that is induced by IL-1β. Furthermore, our observations indicated that miR-382-3p inhibited the expression of Toll-like receptor 4 (TLR4), Myeloid differentiation primary response 88 (MyD88) and nuclear factor κB (NF-κB) in IL-1β-stimulated chondrocytes, while CX43 overexpression could partly reverse these decreases. In conclusion, miR-382-3p participated in OA may through the TLR4/MyD88/NF-κB signaling pathway by directly targeting CX43.     

Bone marrow mesenchymal stem cells-derived exosomal microRNA-16-5p restrains epithelial-mesenchymal transition in breast cancer cells via EPHA1/NF-κB signaling axis

ObjectiveThis study intends to conquer the mystery of microRNA-16-5p/erythropoietin-producing hepatocellular A1/nuclear factor-κB signaling (miR-16-5p/EPHA1/NF-κB signaling) in breast cancer.MethodsExpression of miR-16-5p, EPHA1 and NF-κB signaling-related proteins were detected. Gene overexpression or silencing was used to examine the biological roles of bone marrow mesenchymal stem cells (BMSCs)-derived exo-miR-16-5p in breast cancer. The effect of exo-miR-16-5p on tumorigenesis of breast cancer was confirmed by the xenograft nude mouse model.ResultsLow miR-16-5p and high EPHA1 expression were examined in breast cancer. BMSCs-derived exosomes, up-regulated miR-16-5p or down-regulated EPHA1 restrained epithelial-mesenchymal transition (EMT) of breast cancer cells and tumor growth in nude mice. Down-regulated miR-16-5p or up-regulated EPHA1 activated NF-κB signaling. Knockdown of EPHA1 or inhibition of NF-κB signaling reversed the effects of down-regulated miR-16-5p on breast cancer cells.ConclusionBMSCs-derived exosomal miR-16-5p hinders breast cancer cells progression via EPHA1/NF-κB signaling axis.