长链非编码RNA在非小细胞肺癌诊断及治疗中的研究进展

长链非编码RNA(LncRNA)是一种长度大于200个核苷酸无编码蛋白质功能的RNA分子.LncRNA在表观遗传的调控、细胞周期的调控、细胞分化的调控以及剂量补偿效应中都发挥着重要作用,因此LncRNA的异常表达与肺癌的发生发展密切相关,有望成为肺癌早期诊断和治疗中有效的生物标志物.本文对LncRNA在非小细胞肺癌的发...     

Long noncoding RNA CCDC26 as a potential predictor biomarker contributes to tumorigenesis in pancreatic cancer

Pancreatic cancer (PC) is the fourth most common cancer worldwide and has the least patient survival rate of any cancer. Emerging studies have demonstrated that long noncoding RNAs (lncRNAs) were present in cancer patients and have shown great potential as powerful markers and therapeutic targets. However, little is known about the role of lncRNAs in PC. The present study aimed to investigate the expression pattern, clinical significance and biological function of lncRNA CCDC26 (CCDC26) in PC. With quantitative real-time PCR, we analyzed CCDC26 expression levels in 40 PC patients. We found that the CCDC26 expression was significantly higher in PC tissues than in normal tissues. CCDC26 levels were correlated with tumor size, tumor number, and reduced overall survival (OS). Univariate and multivariate analysis showed that CCDC26 expression is an independent prognostic factor of OS in patients with PC. Additionally, ROC^AUC of CCDC26 was up to 0.663, implicating that CCDC26 could be a diagnostic marker for distinguishing PC from normal. Knockdown of CCDC26 expression by small interfering RNA significantly promoted growth arrest and apoptosis. Moreover, we found that the expression of CCDC26 was positively correlated with PCNA and Bcl2. Our data suggest that CCDC26 may be identified as a novel oncogene in PC, and responsible for growth and apoptosis of cancer cell, partly by regulating the PCNA and Bcl2 expression. This work provides a novel biomarker and therapeutic target of PC for cancer clinic in future.     

MiR-101在乳腺癌中的表达及其意义

目的：探讨miR-101在乳腺癌组织中的表达变化。方法：收集乳腺癌组织及对应的癌旁组织,以qRT-PCR方法测定miR-101在乳腺癌组织中的表达变化。在乳腺癌细胞中转染miR-101 mimics、mimics control,以qRT-PCR方法检测上调效果,MTT方法测定细胞增殖变化,流式细胞术测定细胞凋亡变化,Transwell小室测定细胞迁移和侵袭数目变化,蛋白质印迹法测定细胞中cleaved caspase-3和MMP-2蛋白表达变化。结果：miR-101在乳腺癌组织中的表达水平明显低于癌旁组织(P<0.05)。与miR-NC比较,miR-101细胞中miR-101表达水平升高,细胞增殖能力降低,细胞凋亡率升高,细胞侵袭和迁移数目下降,细胞内的cleaved caspase-3蛋白水平表达升高,MMP-2蛋白表达水平减少(P<0.05)。结论：MiR-101在乳腺癌组织中表达下调,上调miR-101抑制乳腺癌细胞增殖、侵袭和迁移并诱导细胞凋亡。     

长链非编码RNA THRIL与疾病关系研究进展

长链非编码RNA(lncRNA)TNF-α和异质性胞核核糖核蛋白L(hnRNPL)相关的免疫调节lncRNA(THRIL)与hnRNPL结合形成功能性THRIL-hnRNPL复合物,结合在TNF-α的启动子上进而调节TNF-α的表达。研究表明THRIL可能通过调节TNF-α的表达参与多种炎症性疾病、肿瘤和其他疾病的发生与进展,THRIL可能成为疾病药物治疗的新靶点。该文主要综述THRIL在多种疾病中的表达水平和可能的调节机制。     

长链非编码RNA在肝细胞肝癌中的研究进展

肝细胞肝癌(HCC)是肝癌最常见的病理类型,患者病死率高。对HCC发生发展机制的认知局限是其不良预后的重要原因。长链非编码RNA(lncRNA)是基因调控的重要组成部分,在不同疾病患者和不同组织中的表达具有特异性。近年来,lncRNA在癌症发生发展中作用的研究逐渐深入,这为HCC早期诊断、病情控制和预后评估提供了新的方法和思路。本文就长链非编码RNA在HCC中的研究进展作一综述。     

LncRNA DCST1-AS1结合ALDOA促进三阴性乳腺癌细胞的侵袭

目的 探索长链非编码RNA(LncRNA)DCST1-AS1结合果糖二磷酸醛缩酶A(fructose-bisphosphate aldolase A,ALDOA)对三阴性乳腺癌细胞(MDA-MB-231)侵袭的影响.方法 采用RNA pulldown试验、质谱分析和RNA免疫共沉淀试验检测并分析DCST1-AS1与AL...     

Long noncoding RNA CCHE1 indicates a poor prognosis of hepatocellular carcinoma and promotes carcinogenesis via activation of the ERK/MAPK pathway

Survival of patients with hepatocellular carcinoma (HCC) remains poor, which is largely attributed to active carcinogenesis. Accumulating evidence implies that long noncoding RNAs (lncRNAs) could play a pivotal role in cancer biology. However, the clinical valueand biological significance of CCHE1 in HCC carcinogenesis remains to be discovered. Expression of CCHE1was analyzed in 112 HCC tissues and cell lines by qRT–PCR. The higher expression of CCHE1 was significantly correlated with tumor number, tumor size and TNM stage. Multivariate analyses revealed that CCHE1 expression served as an independent predictor for overall survival. Moreover, the effect of CCHE1 on proliferation was evaluated by MTT assays, and cell apoptosis was detected by flow-cytometric analysis. Further experiments demonstrated that CCHE1 knockdown significantly promoted growth arrest and cell apoptosis. Importantly, we further confirmed that ERK/MAPK pathway was found to be inactivated in the HCC cells after CCHE1 knockdown. To our knowledge, this is the first report showed that the role and the mechanism of CCHE1 in the progression of HCC. Together, these results suggest that lncRNA CCHE1 may serve as a candidate prognostic biomarker and target for new therapies in human HCC.     

长链非编码RNA在肿瘤发生及发展中的作用机制

长链非编码RNA(lncRNA)是一类转录本长度＞200个核苷酸的非编码RNA(ncRNA),其在肿瘤的发生、发展中发挥重要作用.IncRNA具有多种生物学功能,可以通过诱饵分子、支架分子和向导分子等形式,在表观遗传学水平、转录水平及转录后水平,调控蛋白质编码基因的表达.lncRNA与肿瘤细胞生长和凋亡、侵袭和转移等生物学行为密切相关.进一步阐明IncRNA在肿瘤发生、发展过程中的作用机制,有望为研究者开发肿瘤诊断和治疗的新方法提供思路.笔者拟就lncRNA调控基因表达的作用机制,及其在肿瘤诊断及治疗中的作用进行综述.     

Long noncoding RNA SNHG1 predicts a poor prognosis and promotes hepatocellular carcinoma tumorigenesis

Hepatocellular carcinoma (HCC) is the main cause of cancer mortality worldwide. Its poor prognosis is mainly ascribed to high recurrence rate. Identifying novel prognostic biomarkers and therapeutic targets would be vital for HCC management. Long noncoding RNA (lncRNA) is a class of RNA with various roles in tumorigenesis. The aim of this study was to investigate the clinical significance and functions of lncRNA-small nucleolar RNA host gene 1 (SNHG1) in HCC. In this study, we found SNHG1 was upregulated in HCC tissues in comparison with adjacent liver tissues in both publicly available microarray data and our own cohort. High SNHG1 expression was correlated with large tumor size, poor differentiation, and aggressive BCLC stage. Kaplan-Meier survival analysis demonstrated that high SNHG1 expression predicts poor prognosis of HCC patients. Gain-of-function and loss-of function experiments showed that SNHG1 promotes HCC cells proliferation, cell cycle progression, and inhibits HCC cells apoptosis. Further experiments revealed that SNHG1 promotes HCC cells proliferation through inhibiting p53 and p53-target genes expression. Collectively, our results demonstrated the clinical prognostic significance and roles of SNHG1 in HCC, and suggested that SNHG1 may be considered as a prognostic biomarker and therapeutic target for HCC.     

长链非编码RNA Lnc00478在卵巢癌组织及细胞系中的表达及临床意义

目的 探讨长链非编码RNA(LncRNA)Lnc00478在卵巢癌中的表达及其对卵巢癌生物学行为的影响.方法 收集该院2018-2019年收治的卵巢癌患者病历资料,选择手术后病理诊断为卵巢癌的标本,且癌旁组织未检测到癌细胞的标本80例,采用实时荧光定量PCR检测卵巢癌组织及癌旁组织中Lnc00478的表达水平,分析其表...     

Long noncoding RNA HULC predicts poor clinical outcome and represents pro-oncogenic activity in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is one of the leading causes of cancer-related mortality, and responds badly to existing treatment. Thus, it is of urgent need to identify novel prognostic markers and therapeutic targets of DLBCL. Emerging studies have implicated that long noncoding RNAs (lncRNAs) are differentially expressed in various tumors and play an important role in the development of cancer. Previously, our group has reported that the novel lncRNA HULC has important biological function and clinical potential in human pancreatic cancer. Here, we investigated the expression of HULC in a cohort of DLBCL to assess its expression pattern, clinical value and molecular mechanism. Firstly, we found that HULC was remarkably overexpressed in both DLBCL tissues and cell lines. Moreover, we illustrated that HULC was closely related to DLBCL characteristics, such as Ann Arbor stages, B symptoms, CHOP-like treatment, rituximab and IPI. Importantly, we verified that HULC was an key predictive factor for DLBCL diagnosis and prognosis from sizable samples through the long time follow-ups. Furthermore, we reveal that the HULC knockdown could significantly arrest cell proliferation and induce apoptosis by repressing cyclin D1 and Bcl-2 in DLBCL cells. Our results suggested that HULC could represent a novel indicator of poor prognosis and may be served as a potential target for the diagnosis and gene therapy of DLBCL.     

胃癌患者血清外泌体中DANCR表达及其临床意义

目的检测胃癌患者血清外泌体(exosome)中抗分化非编码RNA(DANCR)的表达水平并分析其临床应用价值。方法采用实时荧光定量RT-PCR检测胃癌细胞培养上清和胃癌患者血清exosome中DANCR表达水平,分析其与临床病理资料的相关性,绘制ROC曲线评价其诊断效能。结果 DANCR在人胃癌细胞系HGC-27中表达水平(4.43±0.37)明显高于胃黏膜上皮细胞(1.01±0.01),差异有统计学意义(P0.05)。HGC-27细胞培养上清exosome中DANCR表达水平(3.06±0.14)明显高于GES-1细胞(1.01±0.20),差异有统计学意义(P0.05)。DANCR在胃癌患者血清exosome中的平均含量[5.060(1.380,22.785)]较胃良性疾病患者[0.535(0.340,1.380)]和体检健康者[1.200(0.605,1.655)]明显升高(Z分别为-3.409,-4.229,P均0.01),且与肿瘤大小、TNM分期以及淋巴结转移相关。胃良性疾病患者与体检健康者相比,血清exosome中DANCR含量差异无统计学意义(Z=-1.308,P0.05)。胃癌患者血清exosome中DANCR的ROC曲线下面积(AUCROC)为0.777,95%可信区间(CI)为0.678~0.876,cut-off值2.50,敏感性为68.6%,特异性为84.4%。结论胃癌患者血清exosome中DANCR表达水平升高,有望成为胃癌诊断的新指标。     

肿瘤抑素抗肿瘤相关肽对人卵巢癌细胞作用的体外研究

目的探讨肿瘤抑素（Tumstatin）185-203位氨基酸（19肽）对卵巢癌细胞（SKOV3）的治疗作用。方法使用NTS、Annexin／PI和蛋白印迹的方法检测肿瘤抑素19肽对SKOV3细胞增殖和凋亡的影响，以及Bcl-2、BAX等凋亡相关蛋白的表达情况。检测了19肽对SKOV3细胞侵袭能力的影响，同时应用RT-PCR的方法检测基质金属蛋白-2（matrix metallopmteinase-2，MMP-2）、组织金属蛋白酶抑制物-2（tissue inhibitors of metallopmteinase-2，TIMP-2）和膜型基质金属蛋白-1（membrane-type 1 matrix metalloproteinase，MT1-MMP）mRNA表达量的变化情况。结果19肽能够有效抑制SKOV3细胞的增殖，诱导细胞凋亡，而降低Bcl-2的表达，激活caspase通路可能是其诱导细胞凋亡的分子机制之一。此外该19肽能够有效抑制SKOV3细胞的侵袭，这与抑制MT1-MMP的表达进而抑制MMP-2的膜结合活性相关。结论肿瘤抑素19肽可以通过诱导凋亡和抑制细胞侵袭对体外培养的SKOV3产生杀伤和抑制作用。