简介：AbstractBackground:Deregulation of miRNA-21 expression has been reported to be associated with vascular smooth muscle behavior and cytoskeletal stability. This study is aimed to investigate the density of serum miRNA-21 in patients with different phases of intracranial aneurysms (IAs) and explore its warning function for IA rupture.Methods:A total of 16 in 200 IA patients were selected and categorized into 4 groups based on the phase of IA. Microarray study was carried out using serum miRNA and differentially expressed miRNAs were identified. Another 24 samples from a cohort of 360 patients were added and real-time polymerase chain reaction (RT-PCR) was performed on expanded sample size (n = 40) for miRNA-21 validation. Potential gene targets of miRNA-21 were screened out from Gene Ontology (GO) database and literatures.Results:Microarray study identified 77 miRNAs with significantly different expression levels between experimental groups and the control group. RT-PCR assays validated significant downregulation of miRNA-21 in experimental groups, among which miRNA-21 expression level of daughter aneurysm group decreased the most. Bioinformatic analyses revealed that several target genes related with miRNA-21 may be involved in IA formation and rupture.Conclusions:This study suggested that miRNA-21 had a protective effect for intracranial vascular wall against remodeling and warning function for intracranial aneurysm rupture. Significant suppression of serum miRNA-21 in IA patients may provide diagnostic clues for aneurysm rupture and guide clinical intervention.

简介：摘要目的分析血清microRNA-21、可溶性人类主要组织相容性复合体Ⅰ类相关链A(sMICA)水平检测在食管鳞状细胞癌诊断中的应用价值。方法抽取2018年6月至2019年6月郑州市第一人民医院收治的50例食管鳞状细胞癌患者，以荧光定量聚合酶链式反应检测microRNA-21，以酶联免疫吸附法检测sMICA。比较不同分化程度、TNM分期患者血清microRNA-21、sMICA水平。比较有无淋巴结转移患者血清microRNA-21、sMICA水平。随访1年，比较存活患者与死亡患者血清microRNA-21、sMICA水平。结果低分化患者血清microRNA-21、sMICA水平高于中分化患者，中分化患者上述指标水平高于高分化患者(P<0.05)。IV期患者血清microRNA-21、sMICA水平高于Ⅲ期患者，Ⅲ期患者上述指标水平高于Ⅱ期患者，Ⅱ期患者上述指标水平高于Ⅰ期患者(P<0.05)。淋巴结转移患者血清microRNA-21、sMICA水平高于无淋巴结转移患者(P<0.05)。随访1年，50例患者中死亡18例(36.00%)，存活32例(64.00%)。死亡患者血清microRNA-21、sMICA水平高于存活患者(P<0.05)。结论食管鳞状细胞癌患者机体血清microRNA-21、sMICA水平普遍呈高表达状态，分期晚、分化差、生存期短的患者表达水平更高。

简介：摘要目的构建一种太赫兹（THz）超材料传感方法用于microRNA-21（miRNA-21）的信号放大检测。方法首先构建THz超材料传感方法，并用聚丙烯酰胺凝胶电泳及zeta电位验证方法的可行性；对传感器检测条件进行优化之后，对不同浓度的miRNA-21以及其他不同的miRNAs进行检测，并与其他microRNA检测方法进行比较；最后，对该传感器的回收率进行了评价。结果在最优实验条件下，通过双链特异性核酸酶（DSN）循环识别与滚环扩增（RCA）的双重信号放大策略，该THz超材料传感器对靶标miRNA-21的响应范围为10 fmol/L至10 nmol/L，检测限为8.49 fmol/L。并且该传感器具有较好的特异性，具备了从多种miRNAs中识别靶标miRNA-21的能力，并且在商业化人血清样本中的回收率可达94.33%到115.33%。结论该THz传感器可以实现靶标miRNA-21的高灵敏、高特异性检测，具备了在miRNA相关疾病无标记诊断与早期预警的潜力。

简介：摘要目的研究肝母细胞瘤HUH-6株与正常肝LO2细胞株microRNA-21及其靶基因PDCD4和PTEN表达的差别；研究抑制microRNA-21表达后肝母细胞瘤HUH-6细胞株中microRNA-21及其靶基因PDCD4和PTEN的变化，以及反义抑制后HUH-6细胞凋亡、细胞增殖周期的变化。方法正常肝LO2细胞株与肝母细胞瘤HUH-6株作为研究对象，将肝母细胞瘤HUH-6细胞株分为3组，包括：空白对照组(正常培养的HUH-6细胞)；microRNA-21抑制组(转染microRNA-21抑制序列的细胞)；阴性对照组(转染无关序列的HUH-6细胞)。运用实时荧光定量PCR技术分析各组细胞中的microRNA-21的表达水平。运用流式细胞技术检测反义抑制microRNA-21后HUH-6细胞凋亡以及细胞增殖情况。用Westen-blot检测细胞中PDCD4和PTEN的表达情况。结果与正常肝LO2细胞株相比，肝母细胞瘤HUH-6株microRNA-21表达上调；反义抑制后HUH-6细胞中microRNA-21表达下降；反义抑制后HUH-6细胞增殖率下降，凋亡率增加；反义抑制后HUH-6细胞PDCD4和PTEN表达增加。结论本研究通过细胞实验，发现肝母细胞瘤瘤细胞中microRNA-21表达上调，并可以负性调节靶基因蛋白PDCD4及PTEN蛋白的表达；microRNA-21可能通过PDCD4及PTEN蛋白调节肝母细胞瘤的增殖与凋亡。本研究首次进行microRNA-21在肝母细胞瘤细胞中的表达研究，为microRNA-21及靶基因PDCD4及PTEN在肝母细胞瘤发病机制的研究奠定基础，在肝母细胞瘤的治疗方面具有光明的研究前景。

简介：摘要目的观察microRNA-21（miR-21）敲除对耐伊马替尼的人慢性髓性白血病细胞株K562/G01细胞在增殖、药物敏感性等方面的影响，初步探讨miR-21影响K562/G01细胞伊马替尼敏感性的可能机制。方法运用CRISPR/Cas9技术敲除K562/G01细胞的miR-21，经PCR筛选、Sanger测序鉴定和实时定量PCR检测获得miR-21敲除的单细胞克隆。扩增培养后，采用MTT法、细胞克隆形成实验检测miR-21敲除对K562/G01细胞增殖的影响。使用伊马替尼处理细胞后，用MTT法和Annexin Ⅴ-APC/7-AAD双染流式细胞检测法观察敲除miR-21后K562/G01细胞对伊马替尼的敏感性的变化。Western blot法检测miR-21敲除前后K562/G01细胞PTEN、AKT、p-AKT、PI3K、p-PI3K、P210BCR-ABL、p-P210BCR-ABL蛋白表达量的变化。结果成功构建了3个miR-21敲除的K562/G01单细胞克隆，CRISPR/Cas9介导的突变效率为7.12%~8.11%。miR-21敲除使K562/G01细胞的增殖受抑，野生型和1#、2#、6#单细胞克隆的克隆形成率依次为（57.67±8.25）%、（26.94±5.36）%、（7.17±2.11）%、（31.50±3.65）%，差异有统计学意义（P<0.05）。miR-21敲除使K562/G01细胞对伊马替尼的敏感性增加，野生型和1#、2#、6#单细胞克隆对伊马替尼的IC50值分别为（21.92±1.36）µmol/ml、（3.98±0.39）µmol/ml、（5.38±1.01）µmol/ml、（9.24±1.36）µmol/ml，差异有统计学意义（P<0.05）。miR-21敲除后，其靶基因PTEN的蛋白表达水平未见明显变化，但PI3K、AKT信号分子的活化受到抑制，并且P210BCR-ABL、p-P210BCR-ABL蛋白表达也下调。结论miR-21敲除抑制K562/G01细胞增殖，提高其对伊马替尼的敏感性，这可能是通过抑制PI3K/AKT信号通路和BCR-ABL表达实现的。

简介：摘要目的观察microRNA-21（miR-21）敲除对耐伊马替尼的人慢性髓性白血病细胞株K562/G01细胞在增殖、药物敏感性等方面的影响，初步探讨miR-21影响K562/G01细胞伊马替尼敏感性的可能机制。方法运用CRISPR/Cas9技术敲除K562/G01细胞的miR-21，经PCR筛选、Sanger测序鉴定和实时定量PCR检测获得miR-21敲除的单细胞克隆。扩增培养后，采用MTT法、细胞克隆形成实验检测miR-21敲除对K562/G01细胞增殖的影响。使用伊马替尼处理细胞后，用MTT法和Annexin Ⅴ-APC/7-AAD双染流式细胞检测法观察敲除miR-21后K562/G01细胞对伊马替尼的敏感性的变化。Western blot法检测miR-21敲除前后K562/G01细胞PTEN、AKT、p-AKT、PI3K、p-PI3K、P210BCR-ABL、p-P210BCR-ABL蛋白表达量的变化。结果成功构建了3个miR-21敲除的K562/G01单细胞克隆，CRISPR/Cas9介导的突变效率为7.12%~8.11%。miR-21敲除使K562/G01细胞的增殖受抑，野生型和1#、2#、6#单细胞克隆的克隆形成率依次为（57.67±8.25）%、（26.94±5.36）%、（7.17±2.11）%、（31.50±3.65）%，差异有统计学意义（P<0.05）。miR-21敲除使K562/G01细胞对伊马替尼的敏感性增加，野生型和1#、2#、6#单细胞克隆对伊马替尼的IC50值分别为（21.92±1.36）µmol/ml、（3.98±0.39）µmol/ml、（5.38±1.01）µmol/ml、（9.24±1.36）µmol/ml，差异有统计学意义（P<0.05）。miR-21敲除后，其靶基因PTEN的蛋白表达水平未见明显变化，但PI3K、AKT信号分子的活化受到抑制，并且P210BCR-ABL、p-P210BCR-ABL蛋白表达也下调。结论miR-21敲除抑制K562/G01细胞增殖，提高其对伊马替尼的敏感性，这可能是通过抑制PI3K/AKT信号通路和BCR-ABL表达实现的。

简介：AbstractPreoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.

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简介：摘要微小RNA（miRNA）广泛存在于神经系统，可影响突触可塑性、神经炎症、自噬、氧化应激和毒性蛋白聚集等病理生理过程，调节学习、记忆等高级认知功能，参与阿尔茨海默病、术后认知障碍等认知障碍相关疾病的病理过程。此外，外周miRNA动态变化与中枢神经系统miRNA相似，因此有望成为早期检测和评估认知障碍相关疾病进展的潜在生物学标志物。本文综述了miRNA调控高级认知功能的分子机制和认知障碍相关疾病的病理机制，以及外周miRNA作为认知障碍相关疾病潜在生物学标志物的临床应用进展。

简介：AbstractIn recent years, an increasing number of young women have been diagnosed with cancer, including some nulliparous women. Therefore, many young patients with early-stage cancer desire to preserve fertility after cytotoxic oncological treatments. It is important to develop a multidisciplinary approach to achieve the best outcomes for each patient. On the other hand, there has been a sharp increase in microRNAs (miRNAs) as potential biomarkers for the diagnosis, prognosis, and evaluation of treatment efficacy of several diseases. MiR-543 has been reported to affect the pathogenesis and progression of diseases via complex mechanisms. Understanding the regulatory role of miR-543 may aid comprehension of the pathogenesis and treatment of a broad range of diseases. Therefore, we provide an overview of the biogenesis, function, and role of miR-543 in various systems. These results shed light on the anticancer and endometrial protection role of miR-543 in young patients with gynecologic tumors and highlight the clinical potential of miR-543-based applications and related challenges.

简介：摘要角膜新生血管可继发于多种眼部疾病，是影响角膜透明度的主要原因之一。微小RNA(microRNA, miRNA)与病理性角膜新生血管密切相关，可通过调控多种细胞因子的表达和信号传导途径影响角膜新生血管生成。抑制角膜新生血管的miRNA包括miR-184、miR-204，促进角膜新生血管的miRNA包括miR-126、miR-132、miR-21和miR-27a/b。调控这些miRNA有望成为角膜新生血管的治疗方法。对促进角膜血管新生的miRNA，可使用反义miRNA寡核苷酸antagomir抑制内源性miRNA作用。(国际眼科纵览，2020, 44: 192-196)

简介：摘要男性生精过程是一个多步骤、被精密调控的生理过程。单链非编码小RNA分子microRNA(简称miRNA)作为一种基因调控的重要方式，通过抑制和阻碍翻译过程来调节转录后基因沉默，参与各种生理过程。目前已有多项研究证实miRNA介导的转录后基因表达调控与男性精子发生过程存在密切相关性。因此，探讨miRNA在生精过程中的作用及其表达水平变化，有助于进一步了解男性生精的分子机制，寻找针对男性不育有效的生物标志物和治疗策略。本文将从miRNA直接参与或间接影响精子发生2个方面进行综述，总结miRNA在生精过程中的重要作用。

简介：AbstractBackground:Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis.Methods:The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays.Results:Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.Conclusion:The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

简介：摘要孤独症谱系障碍可能是由遗传因素和环境因素共同导致的异质性神经发育障碍性疾病，其患病率呈逐年上升趋势，对家庭和社会带来巨大的经济和精神负担。目前对于孤独症谱系障碍的诊断主要以临床症状及量表测量为主，寻找相对特异的生物标志物对其早期诊断具有重要意义。microRNAs是基因表达转录后的调节因子，是包括神经发育在内的各种细胞发育过程中突出的表观遗传调节剂。它们大量存在于大脑中，其功能障碍与包括孤独症谱系障碍在内的神经精神疾病有关。现就microRNA在孤独症谱系障碍中的表达、靶基因及参与的信号通路的研究进展作一综述。

简介：摘要微小RNA(microRNA，miRNA)是一类长约22个核苷酸的内源性非编码RNA，参与调控细胞增殖、分化、代谢、凋亡的各个方面。小胶质细胞是中枢神经系统的固有免疫细胞，参与介导免疫炎症反应，在众多神经系统疾病的发生、发展及康复过程中扮演重要角色。激活的小胶质细胞能够极化为M1和M2两种类型。M1型主要促进炎症反应的发生，M2型则具有抗炎和促进神经修复的功能。近年来研究发现，miRNA可以调控小胶质细胞的激活极化过程，影响多种神经系统疾病的进程。该文对miRNA的生物学作用及对小胶质细胞激活极化的调控进行综述。

简介：AbstractBackground:Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC).Methods:The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature.Results:Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease.Conclusion:We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

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简介：摘要微小RNA(miRNA)是一种非编码小分子RNA，可以特异性结合目标mRNA的3'非翻译区，从而诱导目标mRNA降解或抑制其翻译，最终影响细胞增生、分化以及凋亡等重要的生物学过程。白内障是全球首位致盲眼病，是一种由晶状体混浊引起的视力下降疾病，包括年龄相关性白内障、糖尿病性白内障、先天性白内障及后发性白内障。近年来研究发现，多种miRNA在晶状体组织中表达，影响晶状体上皮细胞的增生、迁移、上皮-间质转化及凋亡，参与不同类型白内障的发生及发展。本文就不同miRNA在各类型白内障中作用机制的研究进展进行综述，从而为白内障的防治提供新的思路与方法。

简介：摘要microRNA-137（miR-137，微小RNA-137）在许多肿瘤中特别是神经胶质瘤中表达异常，其通过靶向调节CDK6、Rac1、MRGBP、Notch1等基因以及PTP4A3、FOXK1基因介导的信号通路参与神经胶质瘤细胞的增殖、代谢、周期调控、侵袭及患者预后。该文章重点讨论miR-137在神经胶质瘤中的几种特殊的作用机制，进一步了解了miR-137的潜在功能，为神经胶质瘤的诊疗提供新思路。

简介：摘要青春期发育调节过程受多方面因素影响，其机制纷繁复杂。MicroRNA是由21～25个核苷酸组成的短单链RNA，具有调节多种靶基因的表达或翻译的能力，是表观遗传学的主要参与者，在复杂的生物现象中发挥重要的生物学功能。在青春期发育过程中microRNA可通过调控下丘脑-垂体-性腺轴(hypothalamic-pituitary-gonadal axis，HPGA)相关基因的表达而发挥作用。目前研究发现，一些特异性microRNA的缺失或过表达，可引起青春期发育异常(过早或延迟)从而导致生殖功能紊乱，为诊治青春期疾病提供了新方向。该文主要对microRNA参与调控青春期发育的机制进行综述。