环状RNA在免疫炎症反应中的作用及其在口腔疾病中的研究进展

环状RNA（circular RNA，circRNA）由单个RNA分子末端共价形成，无5′及3′核糖核苷酸末端结构，是调控转录后基因表达的新成员。近年研究表明，由不同位置基因组产生的参与转录及转录后基因表达调控的circRNA在人类免疫炎症反应中发挥着至关重要的作用，提示circRNA可能参与牙周炎症的调控过程。除此之外，已有文献报道circRNA还参与其他口腔疾病的生物学过程。文章就circRNA在免疫炎症反应中的作用及其在口腔疾病中的研究进展做一综述。     

circUTRN24通过肝星状细胞自噬介导胆道闭锁肝纤维化

目的 探究胆道闭锁中circUTRN24与自噬途径的关联,以及是否通过自噬参与胆道闭锁的肝纤维化过程。方法 通过RT-qPCR、Western blot分别检测BA组和对照组的肝组织中circUTRN24以及自噬相关蛋白的表达,并进行相关性分析。在细胞水平,通过慢病毒转染使人肝星状细胞系LX-2过表达circUTRN24,Western blot检测转染前后自噬相关蛋白Beclin-1、LC3以及HSC活化相关指标α-SMA、COL-Ⅰ的表达水平。结果 胆道闭锁患儿肝组织中circUTRN24以及自噬相关蛋白Beclin-1的表达明显高于对照组,并且呈正相关关系。过表达circUTRN24的LX-2细胞中自噬相关蛋白Beclin-1、LC3-Ⅱ及HSC活化相关指标α-SMA、COL-Ⅰ均明显升高。结论 circUTRN24可能通过调控肝星状细胞自噬过程促进胆道闭锁肝纤维化的进展。     

Hsa_circ_0003998 Promotes Chemoresistance via Modulation of miR-326 in Lung Adenocarcinoma Cells

Circular RNAs (circRNAs) represent a new class of noncoding RNAs that is involved in the development of cancer. However, little is known about their role in chemoresistance. In the present study, we found that hsa_circ_0003998 expression levels in lung adenocarcinoma (LAD) tissues and docetaxel-resistant cell lines (A549/DTX and H1299/DTX) were upregulated. Knockdown of hsa_circ_0003998 decreased chemoresistance, inhibited proliferation, and enhanced apoptosis in docetaxel-resistant LAD cells. Moreover, by using bioinformatics and luciferase reporter assays, we found that miR-326 was a direct target of hsa_circ_0003998. Functional analysis revealed that miR-326 mediated the effect of hsa_circ_0003998 on chemosensitivity. Our findings provide a molecular insight on understanding drug resistance in LAD cells. Therefore, inactivation of hsa_circ_0003998 or activation of miR-326 could be a novel approach for the treatment of LAD.     

环状RNA在慢性阻塞性肺疾病诊断及预后判断中的研究价值

目的探讨血清环状核糖核酸(circRNA)在慢性阻塞性肺病(COPD)诊断及预后判断中的研究价值。 方法选择连云港市第二人民医院2014年1月至2016年12月收治的80例COPD患者以及同期在该院进行健康体检人群30例为研究对象进行回顾性随机对照研究，其中男性58例，女性52例；年龄61~82岁，平均(70±6)岁。通过Arraystar circRNA芯片筛选获得两组受试者血清样本中差异表达的circRNA，再利用qRT-PCR验证了获得的目标circRNA分子，并结合生物信息学软件对其进行注释和功能预测。 结果本研究对circRNA-001988、circRNA-0000344和circRNA-0000284在COPD组和正常组血清中的表达的差异进行了探究：发现与正常组相比，circRNA-001988和circRNA-0000344在COPD组血清样本中的表达分别下调了(6.54±2.75)倍和(5.94±2.89)倍；circRNA-0000284则在COPD组的血清样本中上调表达了(8.54±3.25)倍。差异均有统计学意义(P<0.05)。 结论血清circRNA可作为COPD诊断和预后判断的生物标志物，具有较好的临床预测价值。     

Circular RNA PPP1CC promotes Porphyromonas gingivalis-lipopolysaccharide-induced pyroptosis of vascular smooth muscle cells by activating the HMGB1/TLR9/AIM2 pathway

ObjectivePorphyromonas gingivalis (Pg) plays a critical role in the occurrence and development of atherosclerosis. Lipopolysaccharide from Pg (Pg-LPS) could lead to pyroptosis of vascular smooth muscle cells (VSMCs) and induce instability of atherosclerotic plaque. Therefore, pyroptosis of VSMCs could promote the process of atherosclerosis. However, the exact mechanism of Pg-LPS-induced pyroptosis of VSMCs is unclear.MethodsWe determined pyroptosis and expression of interleukin (IL)-1β and IL-18 in VSMCs using 4′,6-diamidino-2-phenylindole staining and ELISA after stimulation by Pg-LPS. We established a knockdown plasmid containing the circular (circ)RNA PPP1CC and transfected it into VSMCs. Luciferase assays were performed to reveal the association between microRNAs miR-103a-3p and miR-107 and circRNA PPP1CC.ResultsStimulation of Pg-LPS led to pyroptosis of VSMCs. Knockdown of circRNA PPP1CC relieved the Pg-LPS-induced pyroptosis of VSMCs and suppressed the expression of HMGB1, TLR9, AIM2, and cleaved caspase-1. Luciferase assays showed that PPP1CC directly targeted and competitively adsorbed miR-103a-3p and miR-107, weakening the inhibitory effect of these microRNAs on the expression of HMGB1.ConclusionKnockdown of circRNA PPP1CC relieved Pg-LPS-induced pyroptosis of VSMCs. Pyroptosis of VSMCs appears to promote atherosclerosis and may represent a novel therapeutic target for its treatment.     

非编码RNA调控晶状体上皮细胞死亡在白内障中的作用

非编码RNA（ncRNA）是不编码蛋白质的RNA,其中包括微小RNA（miRNA）、长链非编码RNA（lncRNA）和环状RNA（circRNA）等。ncRNA可以广泛参与细胞增殖、分化、生长以及细胞死亡等重要的生物学过程。ncRNA的异常表达可导致晶状体上皮细胞发生细胞凋亡、焦亡以及自噬异常,使得晶状体透明度下降,从而导致白内障的发生。本文主要对8种miRNA（miR-125b、let-7a、miR-4328、miR-34a、miR-133b、miR138、miR-23b-3p、miRNA-30a）、9种lncRNA（lncRNA MIAT、lncRNA ANRIL、lncRNA PLCD3-OT1、lncRNA GPX3-AS、H19、TUG1、lncRNA PVT1、lncRNA ALB、KCNQ1OT1）以及一种circRNA （circHIPK3）调控晶状体上皮细胞死亡在白内障发生发展中的作用机制最新进展予以综述。     

Hsa_circ_0031787 promotes cell proliferation and invasion in colorectal cancer

ObjectiveCircular RNA (circRNA) has been found to be involved in regulating tumor development. However, the roles and underlying mechanisms of circRNA in colorectal cancer (CRC) development remain unclear. In this study, we investigated the effects of hsa_circ_0031787 on CRC.aMethodsAberrant circRNA expression was explored by the Gene Expression Omnibus (GEO) database, and hsa_circ_0031787 was selected for further study. Hsa_circ_0031787 expression was determined in CRC tissues and cell lines by qRT‐PCR. Cell proliferation was measured by Edu and colony formation assays. Cell invasion was tested by Transwell assays.ResultsHsa_circ_0031787 expression levels in CRC were significantly increased and correlated with advanced TNM stage and lymph node metastasis in CRC patients. Functional assays showed that hsa_circ_0031787 suppression reduced CRC cell proliferation and invasion in vitro and reduced tumor growth in vivo. Furthermore, hsa_circ_0031787 suppression reduced activation of the Wnt/β‐catenin axis in CRC.ConclusionsOur results showed that hsa_circ_0031787 may function as an oncogenic circRNA in CRC progression, thus providing a new potential therapeutic target.     

hsa_circ_0087378在食管鳞状细胞癌组织中的表达及其对患者预后的影响

目的： 探讨 hsa_circ_0087378在食管鳞状细胞癌（ESCC）组织中的表达及其对ESCC患者临床病理指标及预后的影响。 方法： 通过GEO数据库筛选ESCC组织及相应癌旁组织中差异表达的circRNA,采用qPCR法在10例ESCC组织及相应癌旁组织中进行验证。选取河北医科大学第四医院2015年10月至2016年4月收治的90例ESCC患者癌组织及配对癌旁组织标本,通过FISH法检测hsa_circ_0087378 的表达,分析其表达与 ESCC 患者临床病理指标及预后的关系。 结果： GEO数据库及qPCR分析结果显示,hsa_circ_0087378在ESCC组织中表达最明显。FISH结果显示,90例癌旁组织中21例hsa_circ_0087378呈高表达,高表达率为23.3%;90例ESCC组织中有65例hsa_circ_0087378呈高表达,高表达率为72.2%,癌组织中表达明显高于癌旁组织（P<0.05）。hsa_circ_0087378 在 ESCC 组织中的高表达与患者的临床分期和淋巴结转移有关联（P<0.05）,hsa_circ_0087378高表达组ESCC患者的5年总生存率明显低于低表达组患者（P<0.05）。 结论： hsa_circ_0087378在ESCC组织中呈高表达,且与患者的临床分期与淋巴结转移和预后不良有关,其可能是ESCC的治疗靶点。