miRNA-29s在非小细胞肺癌组织中的表达及临床意义

目的 探讨非小细胞肺癌（NSCLC）组织中微小RNA-29s（miR-29s）的表达水平及临床意义。方法 收集2012年1月至2015年12月收治的94例手术切除的NSCLC组织及71例癌旁正常组织,采用实时荧光定量PCR（QPCR）法检测上述组织中miR-29a、miR-29b和mi-29c的表达,比较NSCLC组织及癌旁正常组织中miR-29s的表达水平,Pearson相关分析NSCLC组织中miR-29a、miR-29b和miR-29c表达的相关性,分析NSCLC组织中miR-29s的表达与NSCLC临床病理特征（性别、年龄、TNM分期、组织学类型、分化程度、淋巴结转移及CEA水平）的关系,根据随访资料分析不同miR-29s表达水平与预后的关系。结果 QPCR结果显示,NSCLC组织中miR-29a、miR-29b和miR-29c的表达水平依次为0.413±0.025、0.609±0.039和0.161±0.013,均低于癌旁正常组织,差异有统计学意义（P＜0.05）;NSCLC组织中miR-29a与miR-29b呈正相关（r=0.637,P=0.000）,miR-29a与miR-29c呈正相关（r=0.775,P=0.000）,miR-29b与miR-29c呈正相关（r=0.586,P=0.000）;NSCLC组织中miR-29s表达均与TNM分期有关,miR-29a与肿瘤大小及分化程度有关,miR-29b与分化程度有关,miR-29c与肿瘤大小有关。miR-29a（≥0.354）、miR-29b（≥0.586）和miR-29c（≥0.118）高水平者的中位总生存时间依次为16.4、16.4和16.7个月,均高于低水平者的11.5、9.8和10.5个月,差异有统计学意义（P＜0.05）。结论 miR-29s在NSCLC组织中表达降低,且均与TNM分期及预后有关,可能与NSCLC发生、发展有关,对NSCLC诊断及病情评估有一定价值。     

microRNA-613在恶性肿瘤中的研究进展

微小RNA（microRNA,miRNA）作为一种在恶性肿瘤发生中起到非常重要作用的短链非编码RNA,通过与其靶基因的特异性结合从转录后水平调控肿瘤相关基因的表达。微小RNA-613（microRNA-613,miR-613）定位在人染色体12p13.1,通过对靶基因的调控,参与肿瘤细胞的增殖、分化、凋亡、癌周浸润等恶性进程的调控。近年来研究表明,miR-613在多种肿瘤中异常表达并与肿瘤的临床特征及预后密切相关。鉴于其在恶性肿瘤中的重要作用,miR-613或可成为分子靶向治疗的新靶点。     

CRNDE和miR-181a在结直肠癌中的表达及临床意义

摘 要：［目的］ 研究结直肠癌癌组织中长链非编码RNA（long-noncoding RNA,LncRNA）CRNDE及微小RNA（microRNA,miR）-181a表达及其临床意义。［方法］ 应用荧光实时定量PCR（quantitative real-time PCR,qRT-PCR）检测89例结直肠癌癌组织和癌旁组织中CRNDE及miR-181a的表达,分析组间CRNDE及miR-181a表达差异及两者表达与临床病理特征的关系。Kaplan-Meier生存分析比较不同水平CRNDE、miR-181a患者3年总体生存率（OS）的差异。［结果］ 与癌旁组织相比,结直肠癌组织中CRNDE表达水平明显升高,miR-181a表达水平明显降低（P均<0.05）。结直肠癌癌组织中CRNDE、miR-181a表达与肿瘤分期、肿瘤分化有关（P均<0.05）,与性别、年龄、肿瘤大小、肿瘤位置及淋巴结转移无关（P均>0.05）。癌组织中CRNDE与miR-181a表达呈显著负相关（r=-0.558,P=0.008）。Kaplan-Meier分析表明癌组织中CRNDE高表达患者3年OS明显低于CRNDE低表达者（P<0.05）,而高表达miR-181a与低表达miR-181a患者3年OS无明显差异（P>0.05）。［结论］ 结直肠癌组织中CRNDE表达升高,而miR-181a表达降低,两者均参与结直肠癌的发生发展过程,有可能成为新的肿瘤标志物。     

微小RN A-32在肝细胞癌中的作用

微小RNA（miRNA）参与多种重要的细胞生物学过程,还参与包括肝细胞癌（HCC）在内的多种疾病的发生与发展。近年来研究发现miR-32在多种肿瘤组织中表达异常,miR-32在HCC中表达上调,扮演了“致癌基因”的角色,参与调控体内HCC细胞的细胞周期、凋亡及侵袭转移等多个病理生理过程,并有望成为HCC治疗的新靶点。     

lncRNA BLACAT1靶向结合miR-29a-3p调控甲状腺癌细胞TPC-1的生物学行为

目的:探讨长链非编码RNA BLACAT1(lncRNA BLACAT1)调控microRNA-29a-3p（miR-29a-3p）对甲状腺癌细胞恶性生物学行为的作用及其可能机制。方法:收集2018年06月至2019年03月在我院行甲状腺癌切除术的31例患者的肿瘤组织和相应的癌旁组织。采用qRT-PCR检测lncRNA BLACAT1、miR-29a-3p在甲状腺癌组织、癌旁组织、5种甲状腺癌细胞系（SW579、 PDTC-1、 HMGA1、 TPC-1、 KAT-5）及正常甲状腺细胞Nthy-ori 3-1中的表达水平;调控TPC-1甲状腺癌细胞系中lncRNA BLACAT1、miR-29a-3p的表达,采用CCK-8法检测细胞增殖情况,Transwell法检测细胞的迁移和侵袭能力。用生物信息分析和双荧光素酶报告基因法预测和验证lncRNA BLACAT1与miR-29a-3p的靶向关系。结果:与癌旁组织和正常甲状腺细胞相比,甲状腺癌组织和细胞系中lncRNA BLACAT1的表达水平显著上调,miR-29a-3p的表达水平显著下调（P＜0.05）;过表达lncRNA BLACAT1促进TPC-1细胞的增殖、迁移和侵袭;在甲状腺癌组织中lncRNA BLACAT1的表达水平与miR-29a-3p的表达水平呈负相关（r2 =0.492,P＜0.001）;双荧光素酶分析证实lncRNA BLACAT1能特异性结合miR-29a-3p,并能降低其表达;过表达miR-29a-3p抑制TPC-1细胞的增殖、迁移和侵袭,且miR-29a-3p可以抑制由lncRNA BLACAT1过表达引起的TPC-1细胞增殖、迁移和侵袭能力的增强。结论:lncRNA BLACAT1通过靶向调控miR-29a-3p表达影响甲状腺癌细胞的增殖、迁移和侵袭,从而促进甲状腺癌的发展。     

miR-130在恶性肿瘤中作用研究进展

微小RNA（miRNAs）是一组在转录后水平上调节基因表达的非编码RNA分子,通常结合到mRNA分子上导致靶mRNA降解或翻译抑制。microRNA-130（miR-130）包括miR-130a和miR-130b。研究发现,miR-130在多种机制调控下,在一些肿瘤中发挥癌基因作用,而在另一些肿瘤中发挥抑癌作用,并且与多种肿瘤化疗耐药性有关。本文就miR-130在肿瘤中的作用做一综述。     

miRNA-340和cyclin D1在胃癌组织中的表达及临床意义

目的:探讨胃癌组织中miRNA-340（miR-340）和cyclin D1的表达水平,并分析二者与胃癌患者临床病理参数的关系。方法:选取2019年12月至2020年06月期间我院病理科胃癌手术切除组织及对应癌旁正常胃黏膜组织(距离肿瘤边缘≥5 cm)共60例。采用qRT-PCR检测组织中miR-340的表达水平,采用免疫组化染色检测cyclin D1蛋白表达水平,并分析二者与胃癌患者临床病理参数的关系。结果:胃癌组织中miR-340的表达水平（2.38±0.51）明显低于癌旁正常黏膜组织（2.70±0.54）,差异具有统计学意义（P＜0.05）;胃癌组织中cyclin D1蛋白的表达水平（48.33％）明显高于癌旁正常黏膜组织（16.67％）,差异具有统计学意义（P＜0.05）。胃癌组织中miR-340表达与cyclin D1蛋白表达呈负相关（r=-0.367,P＜0.05）。胃癌组织中miR-340的表达与肿瘤直径、肿瘤的分化程度、浸润深度、临床分期有关（P＜0.05）,cyclin D1蛋白的表达与肿瘤的分化程度、浸润深度、临床分期、神经侵犯及淋巴结转移有关（P＜0.05）。结论:胃癌组织中miR-340和cyclin D1蛋白表达异常,且与不良预后相关,二者联合有望成为胃癌诊疗的潜在生物标志物。     

miR-139抗肿瘤作用与机制

微小 RNA（miRNA）与肿瘤的发生发展密切相关。miR-139是一种具有抑癌作用的miRNA分子,在多种肿瘤组织中表达降低,而过表达 miR-139可通过多种靶基因抑制肿瘤细胞的增殖、迁移和侵袭,并诱导其凋亡。因此,miR-139在肿瘤的临床诊断、治疗及预后判断等方面具有潜在的应用前景。     

肿瘤细胞miR-145表达生物学意义的研究现状

目的:总结国内外研究miR-145与肿瘤关系的文献,评价miR-145在肿瘤发生、发展中的作用.方法:以“miR-NAs、miR-145、肿瘤”为关键词,检索1993-2011年PubMed及CNKI期刊全文数据库.纳入标准:1)miR-145基因结构及生物学特性的研究;2)miR-145与肿瘤发生发展关系的研究;3)miR-145与肿瘤诊断、治疗和预后关系的研究.根据纳入标准,纳入分析30篇文献.结果:miR-145定位于5号染色体肿瘤相关的脆性位点上,在多种组织的恶性肿瘤中miR-145表达明显下调.过表达miR-145可抑制肿瘤细胞增殖及诱导肿瘤细胞凋亡.检测血清中miR-145的含量,有助于肿瘤的早期诊断.肿瘤组织中miR-145的表达量与患者放化疗疗效及预后密切相关.结论:miR-145是一个潜在的肿瘤生物标志,有可能成为肿瘤治疗的新靶标.     

miR-155与SOCS1在非小细胞肺癌中表达及临床意义

摘 要：［目的］ 研究非小细胞肺癌（non-small-cell lung cancer,NSCLC）癌组织中微小RNA（microRNA,miR）-155及细胞因子信号传导抑制因子1（suppressor of cytokine signaling 1,SOCS1）的表达及其临床意义。［方法］ 应用荧光实时定量PCR（quantitative real-time PCR,qRT-PCR）检测96例NSCLC癌组织和瘤旁组织中miR-155与SOCS1的表达。统计分析不同组间miR-155与SOCS1表达差异及其与临床病理特征之间的关系。Cox比例风险模型分析影响NSCLC患者预后的危险因素。［结果］ 癌组织与癌旁组织miR-155相对表达量分别为3.13±0.31、1.05±0.22,SOCS1相对表达量分别为1.26±0.25、4.02±0.33。与癌旁组织相比,NSCLC癌组织中miR-155表达明显较高,而SOCS1表达明显较低（P均<0.05）。癌组织中miR-155及SOCS1表达与肿瘤分期有关（P＜0.05）,而与性别、年龄、病理类型、肿瘤大小、组织学分级及淋巴结转移无关（P均>0.05）。96例NSCLC患者随访3～36个月,中位随访时间23.2个月,高miR-155表达组患者3年OS明显低于低表达组（χ2=4.315,P=0.034）,低SOCS1表达组患者3年OS明显低于高表达组（χ2=3.924,P=0.048）。NSCLC癌组织中高miR-155表达、低SOCS1表达、高肿瘤TNM分期是影响患者生存预后的独立危险因素。［结论］ NSCLC癌组织中miR-155表达升高,SOCS1表达降低,两者均与与肿瘤分期有关,有希望成为NSCLC新的肿瘤标志物。     

胃癌中微小RNA相关研究进展

近期大量研究发现微小RNA在胃癌的发展、诊断、治疗与预防等方面都起着关键性作用.已有报道证实miR-451可以作为一种有用的生物标志物用于胃癌的筛查,miR-203、miR-21可能成为胃癌诊断的标志物.微小RNA既可以发挥癌基因作用,也可以发挥抑癌基因作用,如miR-141通过对正成纤维细胞生长因子受体2基因表达的抑制来发挥抑癌基因的作用.     

Involvement of MicroRNA-198 Overexpression in the Poor Prognosis of Esophageal Cancer

Objective: This study aimed to investigate whether the miR-198 expression level is related to clinicopathologicalfactors and prognosis of esophageal cancer. Methods: MicroRNA was extracted from esophageal cancer patientswho underwent surgery for assessment using the Taqman@ MicroRNA assay. The correlation between miR-198expression and clinicopathological features was analyzed, and the significance of miR-198 as a prognostic factorand its relationship with survival was determined. Results: MicroRNA-198 (miR-198) expression was higher inpatients with poor prognosis than those with good prognosis (P < 0.05). Kaplan-Meier analysis results showedthat the miR-198 expression level had a significant correlation with survival time (P = 0.030) and that patientswith a higher expression of miR-198 had a shorter survival time. Cox multi-factor model analysis showed thatpatient prognosis (P = 0.014), tumor length (P = 0.040) and expression (P = 0.012), and survival time had asignificant correlation; the corresponding risks were 7.268, 1.246, and 3.524, respectively. Conclusion: miR-198 overexpression is involved in the poor prognosis of esophageal cancer and can be used as a biomarker forselection of cases requiring especial attention.     

MicroRNA-135b regulates apoptosis and chemoresistance in colorectal cancer by targeting large tumor suppressor kinase 2

Colorectal cancer remains the third most common cause of death from cancer worldwide. MicroRNA emerges as a good area of research for current cancer therapy. Here, we identified miR-135b to be a contributor to anti-apoptosis and chemoresistance in colorectal cancer. We observed high levels of miR-135b in colorectal cancer cell lines and clinical tissues, compared to colorectal epithelium cell line and noncancerous tissues. Furthermore, enforced expression of miR-135b attenuated doxorubicin-induced apoptosis in colorectal cells. (Doxorubicin alone can trigger significant apoptosis). In elucidating the molecular mechanism by which miR-135b participate in the regulation of apoptosis and chemoresistance in colorectal cancer, we discovered that large tumor suppressor kinase 2 (LATS2) is a direct target of miR-135b. The role of miR-135b was confirmed in colorectal tumor xenograft models. The growth of established tumors was suppressed by an inhibition of miR-135b expression and enhanced apoptosis was further assessed by TUNEL assay. Taken together, our results reveal that miR-135b and LATS2 axis may be a novel therapeutic target for colorectal cancer.     

DNMT1-dependent suppression of microRNA424 regulates tumor progression in human bladder cancer

The aim of this study was to examine the role of miRNAs regulation by DNMT1 and its underlying mechanisms in bladder cancer. The choice of target miRNAs was based on the analysis of a TaqMan MicroRNA Panel assay. The role of target miRNA in tumor behavior and the related signaling pathways were assessed using the human bladder cancer cell lines. We also evaluated the predictive power of the target miRNA and its link to DNMT1 from 124 clinical bladder cancer specimens. Our results revealed that the miR-424 level is significantly increased when blocking DNMT1 in bladder cancer cells. From the clinical specimen analysis, the staining of miR-424 was inversely correlated with DNMT1 immunoreactivity. The lack of miR-424 expression was significantly linked to aggressive tumor growth, advanced clinical stage and poor prognosis in bladder cancer. Increased miR-424 suppressed the tumor growth rate and invasion ability determined in vitro and in vivo. Furthermore, the EGFR pathway plays a role in the transmission of the miR-424 signal that regulates cell growth and the epithelial-to-mesenchymal transition. These results highlight a potential role for miR-424 as a molecular predictor and therapeutic target in bladder cancer.     

Monitoring microRNAs Using a Molecular Beacon in CD133+/CD338+ Human Lung Adenocarcinoma-initiating A549 Cells

Lung cancer is the most common causes of cancer-related deaths worldwide, and a lack of effective methodsfor early diagnosis has greatly impacted the prognosis and survival rates of the affected patients. Tumor-initiatingcells (TICs) are considered to be largely responsible for tumor genesis, resistance to tumor therapy, metastasis,and recurrence. In addition to representing a good potential treatment target, TICs can provide clues for the earlydiagnosis of cancer. MicroRNA (miRNA) alterations are known to be involved in the initiation and progressionof human cancer, and the detection of related miRNAs in TICs is an important strategy for lung cancer earlydiagnosis. As Hsa-miR-155 (miR-155) can be used as a diagnostic marker for non-small cell lung cancer (NSCLC),a smart molecular beacon of miR-155 was designed to image the expression of miR-155 in NSCLC cases. TICsexpressing CD133 and CD338 were obtained from A549 cells by applying an immune magnetic bead isolationsystem, and miR-155 was detected using laser-scanning confocal microscopy. We found that intracellular miR-155 could be successfully detected using smart miR-155 molecular beacons. Expression was higher in TICsthan in A549 cells, indicating that miR-155 may play an important role in regulating bio-behavior of TICs. Asa non-invasive approach, molecular beacons could be implemented with molecular imaging to diagnose lungcancer at early stages.     

血清MicroRNA及MMP在膀胱癌患者中的变化研究

目的 探讨血清MicroRNA及MMP在膀胱癌患者中的变化情况及其临床价值.方法 选取78例膀胱癌患者作为观察组,并将78名同时期进行体检且健康的同龄人员选为对照组,然后将2组的血清MicroRNA及MMP指标进行分别检测与比较,同时比较不同临床分期及病理分级膀胱癌患者的检测水平,同时以Logistic分析血清MicroRNA及MMP指标与膀胱癌的关系.结果 观察组的血清miR-20a、miR-195及MMP水平均高于对照组,而血清miR-126及miR-200a水平则低于对照组.不同临床分期及病理分级膀胱癌患者的检测水平之间存在统计学差异,P均<0.05.经Logistic分析显示血清MicroRNA及MMP与膀胱癌有密切关系.结论 血清MicroRNA及MMP在膀胱癌患者中的变化较大,其水平受临床分期及病理分级影响较为明显.     

MicroRNA-143 functions as a tumor suppressor in human bladder cancer T24 cells

MicroRNA (miR)-143 and -145 were down-regulated in human bladder cancer T24 cells. The enforced expression of miR-143 induced growth-suppression in T24 cells through down-regulation of ERK5 and Akt expression at translational level, and chemically-modified synthetic miR-143 (miR-143/BP) exhibited a greater growth inhibitory effect than wild-type miR-143. In addition, the synthetic miR-143/BP induced apoptotic cell death in some of the transfected cells. Furthermore, co-treatment with the synthetic miR-143/BP and cisplatin showed the additive growth-suppressing effect on T24 cells. These findings suggest that the chemically-modified synthetic miR-143 functions as a tumor suppressor in T24 cells by targeting ERK5 and/or Akt.     

MicroRNA-490-3p and −490-5p in carcinogenesis: Separate or the same goal?

MicroRNA (miR)-490-3p and miR-490-5p, located on chromosome 7q33, are two independent mature products of miR-490 exerting distinct effects on tumor progression. miR-490-3p and miR-490-5p possess antitumor properties. miR-490-3p dysfunction has been associated with malignancies including colorectal cancer, while the abnormal function of miR-490-5p has been more considerably associated with bladder cancer (for example). At present, there are 30 and 11 target genes of miR-490-3p and miR-490-5p, respectively, that have been experimentally verified, of which the cyclin D1 (CCND1) gene is a common target. Through these target genes, miR-490-3p and miR-490-5p are involved in 7 and 3 signaling pathways, respectively, of which only 2 are shared regulatory signaling pathways. The present review introduces two competing endogenous RNA (ceRNA) regulatory networks centered on miR-490-3p and miR-490-5p. These networks may be important promoters of tumor cell proliferation, invasiveness, metastatic potential and apoptosis. Unlike miR-490-5p, miR-490-3p plays a unique role in promoting cancer. However, both are promising molecular markers for early cancer diagnosis and prognosis. In addition, miR-490-3p was also found to be associated with the chemical resistance of cisplatin and paclitaxel. The present review focuses on the abnormal expression of miR-490-3p and miR-490-5p in different tumor types, and their complex ceRNA regulatory networks. The clinical value of miR-490-3p and miR-490-5p in cancer diagnosis, prognosis and treatment is also clarified, and an explanation for the opposing effects of miR-490-3p in tumor research is provided.