miR-145与结肠癌

微小RNA(microRNA,miRNA,miR)是参与基因转录后调控的非编码小分子RNA。miRNA与人类肿瘤的发生、发展密切相关。研究表明,miR-145在结肠癌中呈低表达,具有抑制结肠癌生长的潜能;miR-145可以调节多个靶基因,同时,其本身又受p53的调控。miR-145可能是肿瘤抑制基因调控网络的关键因子。本文就miR-145与结肠癌的相关研究进展作一综述。     

miR-181b与肿瘤

microRNA(miRNA)是一类在转录后水平调控基因表达的单链非编码小分子RNA。miRNA能够调控机体多种生理和病理过程,如细胞增殖、分化、发育、凋亡、激素分泌和肿瘤形成等。在肿瘤中miR-181b与靶基因结合,作用相关信号通路,促进或抑制肿瘤生长,可作为判断某些肿瘤的生物标志物。对miR-181b与恶性肿瘤的发生、发展机制的研究具有重要意义,可为恶性肿瘤的诊断与治疗提供新的思路。     

miR-218-5p在胃癌细胞和胃癌组织中表达的临床意义及生物信息学分析

目的分析miR-218-5p在胃癌细胞和胃癌组织中的表达,采用生物信息学方法,预测其靶基因并对其信号通路进行富集分析,并利用OncomiR数据库对miR-218-5p在胃癌中的表达与预后关系进行生存分析。方法通过实时荧光定量PCR检测miR-218-5p在不同分化程度的胃癌细胞和正常细胞、胃癌组织和癌旁组织中的表达,分析其临床意义。在miRecords网站数据库选择3个以上软件在线预测其靶基因,取其交集,运用DAVID6.7数据库,对其靶基因参与的信号通路进行富集分析。采用OncomiR数据库分析miR-218-5p在胃癌组织相对于癌旁组织中的表达,并利用OncomiR和cBioportal数据库分别进行miR-218-5p在胃癌组织中的表达与预后生存期的分析。结果miR-218-5p在不同分化程度的胃癌细胞中表达下调。相对于癌旁组织,miR-218-5p在胃癌组织中也明显下调,miR-218-5p的下调与胃癌淋巴结转移(P<0.001)及TNM分期(P<0.001)具有相关性。生物信息学分析显示,miR-218-5p的靶基因富集在与肿瘤相关的多个信号通路中,且其在胃癌中的表达与胃癌患者预后具有一定相关性(P=0.01632)。结论miR-218-5p在胃癌中表达下调,起到潜在的抑癌作用,可能成为新的治疗靶点和预后标志物。     

miR-92a与其靶基因的研究进展

微RNA-92a(microRNA-92a, miR-92a)是在进化中高度保守的致病微RNA，属于微RNA-17-92基因簇成员，参与调控细胞增殖、凋亡及分化等生物学活动。最近研究发现，miR-92a表达紊乱与疾病发生相关，主要通过调控靶基因或靶蛋白发挥致病作用。目前与miR-92a相关的研究主要集中在恶性肿瘤领域，且已发现其高表达与癌细胞恶性及肿瘤对放化疗敏感性降低相关。miR-92a靶向靶基因或靶蛋白致病及其与放化疗的关系，是近年来的研究热点。基于此，该文将miR-92a靶向靶基因或靶蛋白致病及其对化学治疗影响的最新研究进行了综述，以期对临床疾病诊疗提供靶标。     

微小RNA-31在肿瘤中的作用研究进展

微小RNA-31 (miR-31)是在动物和人体组织中广泛存在的一种多功能miRNA,可调控靶基因的表达并参与细胞增殖、分化和凋亡等生理、病理过程。miR-31与肿瘤的发生发展密切相关。miR-31可作为抑癌或促癌基因表达于各个肿瘤中,并在肿瘤细胞增殖、侵袭和迁移等多个生物学过程中发挥重要作用。因此,miR-31有望成为恶性肿瘤的新型生物标志物和治疗靶点。本文就miR-31在恶性肿瘤中的作用机制、治疗预后等方面的研究进展进行综述,以期为恶性肿瘤的早期诊断及个性化治疗提供策略。     

miR-361在心血管疾病的研究进展

微小RNA(microRNA, miRNA)是一类内源性单链非编码RNA分子,长度约21~23个核苷酸,通过结合靶基因的3'非翻译区转录调控基因的表达,参与细胞增殖、分化、凋亡等生物学活动,对机体内不同组织细胞的生长、发育产生重要影响。随着近几年对miRNA-361的深入研究,发现miRNA-361在心血管方面具有重要作用,并影响疾病的发展及预后。本文通过总结miR-361在心血管疾病如动脉粥样硬化(AS)、急性心肌梗死(AMI)、血管瘤(HA)、肺动脉高压(PAH)、 静脉血栓栓塞症(VTE)、盐敏感高血压(SSH)等的表现,对近几年miR-361的相关机制与最新进展进行综述,期望未来能在miR-361方面为心血管疾病的预防、诊断和治疗带来新的启发。     

miR-17-92基因簇与肿瘤

微小RNA(miRNA)是近年来新发现的与肿瘤的发生发展密切相关的一类RNA。它可通过调控其靶标基因参与的信号通路,影响肿瘤的发生和发展,发挥着类似于癌基因或抑癌基因的功能,因此miRNA失调在肿瘤中起重要作用。较多的研究发现,miR-17-92簇与肿瘤的发生密切相关,具有癌基因和抑癌基因双重功能。本文就miR-17-92簇在肿瘤中的作用机制及功能作一综述。     

青少年肥胖非酒精性脂肪肝患者血清外泌体源性miRNA表达谱的初步研究

目的分析非酒精性脂肪肝(NAFLD)与单纯肥胖对照者血清外泌体微小RNA(miRNA)表达谱的差异,为筛选外泌体源性miRNA作为NAFLD早期诊断标记物提供依据。方法选择5例NAFLD患者(NAFLD组)和5例单纯肥胖患者(对照组),采集外周血血清,使用高通量测序方法测定外泌体源性miRNA表达谱,并通过实时荧光定量PCR验证部分差异性表达的miRNA,预测靶基因及功能分析。结果NAFLD组与对照组相比差异表达的外泌体源性miRNA共30种(P<0.05),当倍比值>2且P<0.05的差异性miRNA有9种,其中5种表达上调(miR-122-5p,miR-3591-3p,miR-335-5p,let-7g-3p和miR-27a-5p),4种表达下调(miR-6753-3p,miR-129-2-3p,miR-6760-5p,miR-6516);对miR-122-5p、miR-335-5p、miR-27a-5p进行实时荧光定量PCR,结果与测序结果一致。差异表达miRNA的功能分析结果提示涉及葡萄糖稳态、脂质代谢、肝脏发育等。结论NAFLD组血清外泌体源性miRNA表达谱与对照组有明显差异,miR-122-5p、miR-335-5p、miR-27a-5p可能参与了NAFLD的发病机制,可以作为NAFLD早期诊断的标记物。     

miR-550a-5p在骨髓增生异常综合征中的表达及其靶基因预测

目的:探讨miR-550a-5p在骨髓增生异常综合征(MDS)患者骨髓中的表达情况并通过生物信息学分析预测靶基因及其功能,为进一步研究miR-550a-5p及其靶基因在MDS发病机制中的作用提供依据。方法:采用realtime PCR技术检测miR-550a-5p在54例MDS患者、16例MDS转化白血病患者及19例健康对照中的表达量,并分析其与临床病理特征(包括染色体情况、骨髓原始细胞比例及外周血血象)的相关性。应用miRBase获得并分析多个物种miR-550的序列特征;应用Microcosm、Miranda和Targetscan预测miR-550a-5p的靶基因,并取预测结果交集,进一步进行基因功能的GO(富集)分析和信号转导通路(Pathway)的富集分析。结果:miR-550a-5p表达量在所有MDS患者骨髓中均比对照组升高:在低危+中危1组中表达量是对照组的1.7倍(P=1.23×10-10);在中危2+高危组中表达量是对照组的1.9倍(P=1.20×10~(-10));在MDS转化为白血病组中的表达量是对照组的2.0倍(P=5.61×10~(-10))。随着MDS疾病危险度增高,miR-550a-5p表达水平逐渐上升,但其表达量与MDS患者的临床病理特征(包括染色体情况、骨髓原始细胞比例及外周血血象)之间无明显相关。利用生物信息学预测miR-550a-5p在MDS中的靶基因,结合文献报道选出了其中2个可能与miR-550a-5p调控MDS发生发展的病理机制有关的靶基因——PDLIM2和PSME1。结论:miR-550a-5p在MDS患者骨髓细胞中呈现出特异性高表达,推测其可能通过调控靶基因PDLIM2和PSME1参与MDS病理生理过程。     

hsa-miR-150-5p的生物信息学分析

目的探讨hsa-miR-150-5p在其基因家族的进化关系及可能介入的生物学过程。方法利用人类miRNA表达数据库(HMED)获得hsa-miR-150-5p在不同组织和疾病中特异性表达丰度信息,运用miRBase、Clustalw2和MEGA5.0分析软件获取hsa-miR-150-5p的染色体定位、碱基序列比对特征和进化规律等基本信息,通过miRDB、PicTar和TargetScan进行靶基因预测,采用基因本体(GO)和代谢通路富集分析(KEGG)对靶基因的生物学功能注释分析,进一步认识hsa-miR-150-5p的生物学功能。结果通过同源性搜索在miRBase数据中获得miR-150基因家族成员的序列36条,分布于23个物种。多序列比对发现miR-150基因家族成员序列碱基保守性很高,其中有16个碱基完全保守,6个碱基相对保守。进化分析表明人类的miR-150与青鳉、三文鱼、钳鱼、斑马鱼的分子系统进化关系较远,与其他18个物种的进化关系较近。对miRDB、PicTar和TargetScan预测的靶基因进行交集后共得到25个靶基因,GO分析结果显示靶基因参与多个信号通路的调节,包括转录因子、锌指蛋白、Toll样受体信号通路的转导蛋白、ATP偶联的离子型通道受体和细胞因子信号传导抑制蛋白等。结论 hsa-miR-150-5p在多种组织和疾病中表达,分布具有组织特异性,可能在机体的多种生理、病理过程中发挥重要作用,并可能通过调控多个靶基因而参与各个信号通路调节。     

miR-139-5p靶基因参与调控人骨肉瘤细胞表型的机制分析

目的 通过生物信息学方法预测miR-139-5 p的靶基因,并对靶基因进行信号通路富集分析,结合蛋白质互作(PPI)网络分析筛选核心基因.方法 使用dbDEMC数据库检索miR-139-5 p在骨肉瘤细胞中的表达,使用miRSystem网站的生物信息学数据库进行miR-139-5 p的靶基因预测,利用DAVID6.8软...     

急性冠脉综合征患者血清miR-361-5p 和COMP 表达水平及其与短期预后的相关性研究

目的　研究急性冠脉综合征（acute coronary syndrome ,ACS） 患者血清微小核糖核酸（micro RNA ,miRNA）-361-5p 和软骨寡聚基质蛋白（cartilage oligomeric matrix protein ,COMP）表达水平及其与短期预后的相关性。方法　选取2020 年1 月～ 2021 年1 月鄂东医疗集团黄石市中心医院收治的170 例ACS 患者为ACS 组,根据Gensini积分分为重度狭窄组（n=41）、中度狭窄组（n=78）和轻度狭窄组（n=51）。另选取同期66 例体检健康者为对照组。qRT-PCR 与ELISA 检测血清miR-361-5p 和COMP 水平;Pearson 相关性分析ACS 患者血清miR-361-5p 和COMP 水平与Gensini 评分的相关性;多因素Logistic 回归分析ACS 患者短期预后不良影响因素,受试者工作特征（ROC）曲线分析血清miR-361-5p 和COMP 水平对ACS 发病和短期预后的预测价值。结果　与对照组比较,ACS 组血清miR-361-5p（0.58±0.21 vs 0.33±0.18）和COMP（143.64±25.23ng/ml vs 112.35±19.09ng/ml）水平均升高,差异有统计学意义（t=8.625,10.277,均P ＜ 0.001）。轻度狭窄组、中度狭窄组和重度狭窄组血清miR-361-5p(0.34±0.11,0.63±0.15, 0.76±0.12)和COMP[118.01（108.29, 125.52）ng/ml,147.71（134.72, 158.63）ng/ml,162.32（158.74, 177.71）ng/ml] 水平依次升高,差异有统计学意义（F=131.941,H=101.001,均P ＜ 0.001）。Pearson 相关性分析显示,ACS 患者血清miR-361-5p和COMP 水平与Gensini 评分呈正相关（r=0.765,0.755,均P ＜ 0.001）。随访3 个月,170 例ACS 患者主要不良心血管事件发生率为13.53%（23/170）,多因素Logistic 回归分析显示,miR-361-5p（OR=1.524,95%CI:1.240 ～ 2.023,P=0.004）、COMP（OR=1.646,95%CI:1.318 ～ 2.075,P=0.001）是ACS 患者短期预后不良的独立影响因素。ROC曲线显示,miR-361-5p 预测ACS 发病和短期预后不良的曲线下面积（AUC）为0.813 和0.776,COMP 预测ACS 发病和短期预后不良的AUC 为0.836 和0.782,miR-361-5p ＋ COMP 联合预测ACS 发病和短期预后不良的AUC 为0.904和0.863。miR-361-5p ＋ COMP 联合预测ACS 发病和短期预后不良的AUC 大于miR-361-5p 和COMP 单独预测,差异均有统计学意义（Z=4.684,4.573;2.494,2.617,均P ＜ 0.05）。结论　ACS 患者血清miR-361-5p 和COMP 水平升高,与冠状动脉狭窄程度密切相关,可作为ACS 发病和短期预后不良的预测指标。     

血清miR-146b-3p、miR-15b-5p、miR-16-5p在良恶性肺结节鉴别诊断、预后评估中的价值

目的探究微小RNA（miR）-146b-3p、miR-15b-5p、miR-16-5p在良恶性肺结节鉴别诊断以及预后评估中价值。 方法前瞻性选择2018年6月至2020年6月期间安徽医科大学第二附属医院收治139例肺结节患者作为研究对象,行病理检查或者穿刺活检后确定患者病灶良恶性,其中良性组75例,恶性组64例。2组患者均测定血清miR-146b-3p、miR-15b-5p、miR-16-5p。分析上述指标在患者良恶性结节诊断上价值,恶性组患者血清miR-146b-3p、miR-15b-5p、miR-16-5p与患者病理特征之间关系。随访评估恶性组患者预后,分析血清miR-146b-3p、miR-15b-5p、miR-16-5p对预后预测价值。 结果良性组患者血清miR-146b-3p、miR-15b-5p显著低于恶性组（P＜0.05）,miR-16-5p显著高于恶性组（P＜0.05）。受试者工作特征（ROC）曲线显示,血清miR-146b-3p、miR-15b-5p、miR-16-5p及各种指标联合对于结节良恶性诊断曲线下面积（AUC）分别为0.803、0.786、0.889、0.962。血清miR-146b-3p、miR-15b-5p、miR-16-5p与分化程度、淋巴结转移、临床分期类型有关（P＜0.05）;Spearman相关性分析显示,血清miR-146b-3p、miR-15b-5p均与分化程度呈显著的负相关,且均有统计学意义（r=-0.534,-0.468;P＜0.05）,均与淋巴结转移呈显著的正相关,且均有统计学意义（r=0.582,0.608;P＜0.05）,均与临床分期类型呈显著的正相关（r=0.486,0.519;P＜0.05）;miR-16-5p与分化程度、淋巴结转移、临床分期分别呈显著的正相关、负相关、负相关（r=0.412,-0.563,-0.657;P＜0.05）,且均有统计学意义。预后不良恶性组患者血清miR-146b-3p、miR-15b-5p显著高于恶性组,miR-16-5p显著高于预后良好患者,且上述差异均有统计学意义（P＜0.05）。ROC曲线显示,血清miR-146b-3p、miR-15b-5p、miR-16-5p及各指标联合对于恶性结节患者预后预测AUC分别为0.799、0.772、0.554、0.837。 结论血清miR-146b-3p、miR-15b-5p、miR-16-5p与肺结节良恶性、恶性结节临床特征以及恶性结节患者预后关系密切,三种血清指标联合用于肺结节良恶性鉴别诊断以及预后预测价值优异。     

Retracted Article: Long non-coding RNA MEG3 inhibits cell proliferation,migration, invasion and enhances apoptosis in non-small cell lung cancer cells by regulating the miR-31-5p/TIMP3 axis

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths. Long non-coding RNA maternally expressed gene 3 (MEG3) has been identified as a tumor suppressor in multiple cancers. However, the regulatory mechanism of MEG3 in NSCLC development is still largely unknown. The expression levels of MEG3, microRNA-31-5p (miR-31-5p) and tissue inhibitor of metalloproteinase 3 (TIMP3) in NSCLC tumors and cells were measured by quantitative real time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, migration and invasion were detected by cell counting kit-8 (CCK-8), flow cytometry, western blotting and transwell assays, respectively. Xenograft mouse models were established by subcutaneously injecting NSCLC cells stably transfected with Lenti-pcDNA or Lenti-MEG3. The interaction between miR-31-5p and MEG3 or TIMP3 was validated by luciferase reporter and RNA immunoprecipitation (RIP) assays. MEG3 and TIMP3 levels were up-regulated, whereas miR-31-5p expression was down-regulated in NSCLC tumors and cells compared with normal tissues and cells. Overexpression of MEG3 repressed cell proliferation, migration and invasion, but induced apoptosis in NSCLC cells. More importantly, MEG3 effectively hindered tumor growth in vivo. Next, luciferase reporter and RIP assays confirmed the interaction between miR-31-5p and MEG3 or TIMP3. Pearson''s correlation coefficient revealed that miR-31-5p was inversely correlated with MEG3 or TIMP3. Rescue experiments indicated that MEG3 regulated TIMP3 expression by sponging miR-31-5p in NSCLC cells. Thus, MEG3 inhibited cell proliferation, migration and invasion, but enhanced apoptosis in NSCLC cells through up-regulating TIMP3 expression by regulating miR-31-5p, indicating novel biomarkers for the therapy of NSCLC.

Non-small cell lung cancer (NSCLC) is a malignant lung cancer and accounts for 80% of lung cancer-related deaths.     

MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors

Introduction: MicroRNA (miRNA) is a small non-coding RNA, which negatively regulates the expression of many target genes, thereby contributing to the modulation of diverse cell fates. Recent advances in molecular biology have revealed the potential role of miRNAs in tumor initiation, progression and metastasis. Aberrant regulation of miRNAs has been frequently reported in a variety of cancers, including gastrointestinal tumors, suggesting that cancer-related miRNAs are promising as novel biomarkers for tumor diagnosis and are potential target genes for cancer gene therapy against gastrointestinal tumors.

Areas covered: The review focuses on the role of specific miRNAs (miR-192/194/215 and miR-7) in the differentiation of gastrointestinal epithelium and on the role of tumor-suppressive (miR-34, miR-143, miR-145) and oncogenic miRNAs (miR-21, miR-17-92 cluster) in gastrointestinal tumors. Furthermore, the potential role of miRNAs as novel biomarkers and target genes for cancer gene therapy against gastrointestinal tumors are discussed. We will also outline the potential clinical application of miRNAs for tumor diagnosis and cancer gene therapy against gastrointestinal tumors.

Expert opinion: Exploration of tumor-related miRNAs would provide important opportunities for the development of novel cancer gene therapies aimed at normalizing the critical miRNAs that are deregulated in gastrointestinal tumors.     

miRNA-192-5p在多发性骨髓瘤中的表达水平及其调控机制研究

目的 探讨miR-192-5 p在多发性骨髓瘤中的表达水平及其调控机制.方法 选取骨髓瘤细胞株U266作为研究对象,利用荧光定量PCR检测多发性骨髓瘤细胞中miR-192-5 p的表达水平;使用生物信息学网站预测miR-192-5 p潜在靶基因USP1并利用双荧光素酶报告实验验证其靶向关系;利用细胞转染实验对多发性骨髓...     

MicroRNAs as potential target gene in cancer gene therapy of gastrointestinal tumors

INTRODUCTION: MicroRNA (miRNA) is a small non-coding RNA, which negatively regulates the expression of many target genes, thereby contributing to the modulation of diverse cell fates. Recent advances in molecular biology have revealed the potential role of miRNAs in tumor initiation, progression and metastasis. Aberrant regulation of miRNAs has been frequently reported in a variety of cancers, including gastrointestinal tumors, suggesting that cancer-related miRNAs are promising as novel biomarkers for tumor diagnosis and are potential target genes for cancer gene therapy against gastrointestinal tumors. AREAS COVERED: The review focuses on the role of specific miRNAs (miR-192/194/215 and miR-7) in the differentiation of gastrointestinal epithelium and on the role of tumor-suppressive (miR-34, miR-143, miR-145) and oncogenic miRNAs (miR-21, miR-17-92 cluster) in gastrointestinal tumors. Furthermore, the potential role of miRNAs as novel biomarkers and target genes for cancer gene therapy against gastrointestinal tumors are discussed. We will also outline the potential clinical application of miRNAs for tumor diagnosis and cancer gene therapy against gastrointestinal tumors. EXPERT OPINION: Exploration of tumor-related miRNAs would provide important opportunities for the development of novel cancer gene therapies aimed at normalizing the critical miRNAs that are deregulated in gastrointestinal tumors.     

miR-146b-5p对骨肉瘤细胞增殖抑制及克隆形成的机制研究

目的　检测骨肉瘤组织中 miR-146b-5p表达，探究其对骨肉瘤（ osteosarcoma，OS）细胞增殖、克隆形成的影响及潜在分子作用机制。方法　选取 2018年 1月～ 2020年 12月内蒙古自治区巴彦淖尔市医院病理科 30组临床骨肉瘤组织及邻近正常组织标本，采用实时荧光定量 PCR实验（ qRT-PCR）法检测组织中 miR-146b-5p表达水平；通过介导转染 miR-146b-5p mimics和 miR-146b-5p ASO分别过表达和敲低 miR-146b-5p表达，探究其对骨肉瘤细胞增殖及克隆形成的影响。通过生物学信息数据库预测 miR-146b-5p的潜在靶基因，荧光素酶实验验证两者结合关系，分析 miR-146b5p对靶基因的调控作用。分析靶基因在骨肉瘤中的表达特征及与 miR-146b-5p的相关性，通过细胞增殖实验验证两者的调控作用，以其探究在骨肉瘤中发挥功能的潜在分子机制。结果　骨肉瘤组织中 miR-146b-5p表达（ 4.096±1.237）显著低于邻近正常组织（ 5.895±0.834），差异有统计学意义（ t=6.605，P＜ 0.001）。miR-146b-5p过表达抑制了骨肉瘤细胞的增殖能力（ t=13.233～ 34.599，均 P＜ 0.01）。miR-146b-5p过表达组克隆形成数目（ 48.912±2.032）较对照组（160.834±9.031）明显降低，差异有统计学意义（ t=20.942，P＜ 0.001）。DUSP16是 miR-146b-5p的潜在靶基因， miR-146b-5p负向调控双特异性磷酸酶（ dual speci.city phosphatase 16, DUSP16）表达。骨肉瘤组织中 DUSP16表达（5.683±0.457）较邻近正常组织（ 4.665±0.531）显著升高，差异有统计学意义（ t=7.959，P＜ 0.001），与 miR-146b5p表达呈负相关（ r=-0.667，P<0.05）。共转染过表达 DUSP16逆转了 miR-146b-5p对骨肉瘤细胞增殖的抑制作用。 miR-146b-5p过表达组 P21水平（ 4.995±0.214）较对照组（ 1.001±0.002）显著升高，差异有统计学意义（ t=32.325，P＜ 0.001）；当共转染 DUSP16过表达后， P21表达（ 0.986±0.012）较单独过表达 miR-146b-5p组（4.995±0.214）显著降低，差异有统计学意义（ t=32.398，P＜ 0.001）。结论　骨肉瘤组织中 miR-146b-5p显著低表达，其过表达抑制了骨肉瘤细胞的增殖及克隆形成； miR-146b-5p通过靶向负调控 DUSP16表达参与 P53信号通路从而在骨肉瘤发生发展起重要作用。     

Retracted Article: Exosomal miR-25-3p derived from hypoxia tumor mediates IL-6 secretion and stimulates cell viability and migration in breast cancer

Hypoxia is a major hallmark of solid tumors and is associated with malignant phenotypes. Exosomal miRNAs derived from hypoxia tumor cells are implicated in the modulation of cancer progression, whereas, the mechanisms underlying the association between hypoxia and exosomal miR-25-3p during breast cancer progression remain to be further clarified. The present study aimed to investigate the role of exosomal miR-25-3p in regulating breast cancer progression. Herein, we found that miR-25-3p expression was increased in hypoxia tumor-derived exosomes a HIF-1α-dependent manner. Hypoxia exosomes markedly stimulated the viability and migration of normoxia breast cancer cells, which was reversed by miR-25-3p depletion. Inhibition of exosomes miR-25-3p lowered hypoxic-induced the expression of IL-6 and NF-κB from THP-1 and RAW264.7 cells in a TLR7/8-dependent way. Treatment of macrophage supernatant (MS) initially incubated with hypoxic-responsed exosomes accelerated the viability and migration of breast cancer cells, and miR-25-3p depletion relieved the stimulatory effects of hypoxic on cell viability and migration. Moreover, miR-25-3p knockdown dramatically suppressed HIF-1α-induced tumor growth in vivo via inactivation of IL-6/STAT3 signaling pathway, reflected by the abated abundances of IL-6 and p-STAT3. These data suggested that absence of exosomal miR-25-3p rescued breast cancer aggressiveness through inhibiting cell viability and migration by regulation of IL-6 secretion from macrophages, providing a potential biomarker for breast cancer treatment.

Hypoxia is a major hallmark of solid tumors and is associated with malignant phenotypes.