长链非编码RNA Gas5在非小细胞肺癌中的表达及意义

目的探讨长链非编码RNA Gas5(lncRNA growth arrest-specific 5,lncRNA Gas5)在非小细胞肺癌(NSCLC)中的临床意义。方法收集2009年2月至2011年2月我院50例NSCLC手术切除标本,qRTPCR检测肿瘤和正常肺组织中Gas5的表达,同时比较肺癌细胞株和正常支气管上皮细胞株中Gas5的表达差异,并分析Gas5与临床病理及预后的关系。结果肺癌组织中的Gas5的表达水平显著低于正常肺组织中的表达水平(P0.001)。肺癌组织中Gas5的表达水平与肿瘤的大小、淋巴结转移及临床分期明显相关(P0.05)。Gas5低表达者生存时间明显低于高表达者,差异有显著统计学意义(P0.05)。结论 LncRNA Gas5在NSCLC组织中表达下调,可能成为NSCLC判断预后的新的分子标记物。     

Analysis of long non-coding RNA expression profiles in gastric cancer

AIM: To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer. METHODS: Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P -values below 0.01 were considered differentially expressed. An independent data set was used to validate the results. RESULTS: With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P -value < 0.01) with the same direction. CONCLUSION: We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.     

长链非编码RNA在癌症中的研究进展

长链非编码RNA(lncRNA)在癌症中扮演重要的角色。基因组关联研究已经发现,大量的lncRNA与各种类型的癌症相关。lncRNA的表达和突变能够促进肿瘤的形成和转移。lncRNA可能具有肿瘤抑制和促进致癌作用。因为lncRNA的基因组表达具有多样性和特异性,所以,lncRNA被认定可以作为新的肿瘤分子标志物和治疗靶点。本文结合国内外最新报道,对lncRNA在癌症中的研究进展作一综述。     

长链非编码RNA与肺癌相关性的研究进展

肺癌是目前全世界发病率和病死率最高的恶性肿瘤.长链非编码RNA(lncRNA)是一类转录本长度超过200 nt的RNA,不能编码任何蛋白质.当前研究提示lncRNA在表观遗传学调控、转录水平调控及转录后调控等层面上发挥重要的调控作用.如今lncRNA与肺癌之间的关联成为一个新的研究热点.研究发现MALAT1、H19、lincRNA p21、lncRNA-SCAL1、BC200与肺癌的发生、发展有密切关系.本文对lncRNA在肺癌中的研究进展进行综述,为肺癌的早期临床诊断、治疗及预后提供参考.     

Value of long non-coding RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy

BACKGROUND Esophageal cancer is a common digestive tract tumor that is generally treated with radiotherapy. Poor responses to radiotherapy in most patients generally result in local radiotherapy failure, so it is essential to find new radiosensitizers that can enhance the response of cancer cells to radiotherapy and improve the survival of esophageal cancer patients with radiation resistance. The long noncoding RNA(lnc RNA) Rpph1 is highly expressed in human gastric cancer tissues, and represses breast cancer cell proliferation and tumorigenesis.However, the expression of lnc RNA Rpph1 in esophageal cancer and its relationship with radio-sensitivity has not been studied.AIM To explore the value of lnc RNA Rpph1 in esophageal cancer and its effect on cancer cell sensitivity to radiotherapy.METHODS Eighty-three patients with esophageal cancer admitted to Qilu Hospital of Shandong University and 90 healthy participants who received physical examinations were collected as research participants. The expression of Rpph1 was determined by q RT-PCR. si RNA-NC and si RNA-Rpph1 were transfected into esophageal cancer cell lines, and cells without transfection were designated as the blank control group. Cell survival was tested by colony formation assays,and the levels of proteins related to apoptosis and epithelial-mesenchymal transitions were determined by Western blot assays. Cell proliferation was assessed by MTT assays, cell apoptosis by flow cytometry, and cell migration by wound-healing assays. Changes in cell cycle distribution were monitored.RESULTSRpph1 was highly expressed in esophageal carcinoma, making it a promising marker for the diagnosis of esophageal cancer. Rpph1 could also be used to distinguish different short-term responses, T stages, N stages, and clinical stages of esophageal cancer patients. The results of 3-year overall survival favored patients with lower Rpph1 expression over patients with higher Rpph1 expression(P 0.05). In vitro and in vivo experiments showed that silencing Rpph1 expression led to higher sensitivity of esophageal cancer cells to radiotherapy, stronger apoptosis in esophageal cancer cells induced by radiotherapy, higher expression of Bax and caspase-3, and lower expression of Bcl-2(Bax, caspase-3, and Bcl-2 are apoptosis-related proteins). Additionally,silencing Rpph1 attenuated radiation-induced G2/M phase arrest, and significantly inhibited the expression of proteins involved in cell proliferation,migration, and epithelial-mesenchymal transition regulation in esophageal cancer cells.CONCLUSION Rpph1 is highly expressed in esophageal cancer. Silencing Rpph1 expression can promote cell apoptosis, inhibit cell proliferation and migration, and increase radio-sensitivity.     

Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle organization

BackgroundThis paper examines the expression, function, and molecular mechanism of long non-coding ribonucleic acid (lncRNA) ARAP1 antisense RNA 1 (ARAP1-AS1) in lung cancer. Specifically, it aims to clarify the molecular mechanism of lncRNA ARAP1-AS1 that affects the occurrence and development of lung cancer, and provide a theoretical basis and molecular targets for targeted therapy or early diagnosis of lung cancer.MethodsFluorescence quantitative detection of lncRNA ARAP1-AS1 expression in lung cancer tissues and cell lines, and methylthiazolyldiphenyl-tetrazolium (MTT), plate cloning experiment, and flow cytometry were used to detect the effect of knockdown of lncRNA ARAP1-AS1 on cell proliferation, clone formation, and the cell cycle, respectively. Western blotting was used to detect the expression of cell cycle-related proteins as well as the effect of knockdown of lncRNA ARAP1-AS1 on lung cancer. Cell proliferation was assessed by a nude mouse subcutaneous tumor formation experiment.ResultsLncRNA ARAP1-AS1 is highly expressed in lung cancer tissues and cells. Knockdown of LncRNA ARAP1-AS1 can significantly inhibit the proliferation and clonal formation of lung cancer cells and induce G0/G1 cell cycle arrest. Knockdown of ARAP1-AS1 can markedly inhibit the expression of cell cycle-related protein cyclin D1, but has no significant effect on the expression of cyclin-dependent kinase (CDK)4 and CDK6. Furthermore, knockdown of ARAP1-AS1 can also notably inhibit the growth of lung cancer cells and substantially reduce the expression of Ki-67 in tumor-bearing tissues in nude mice.ConclusionsLncRNA ARAP1-AS1 is highly expressed in lung cancer. Knocking down of this gene can significantly inhibit cell proliferation in vitro and in vivo, and can also cause G0/G1 cell cycle arrest by inhibiting the expression of cyclin D1.     

长链非编码RNA在肺癌中的调控机制

长链非编码RNA是一类长度大于200个核苷酸,没有蛋白质编码功能的RNA。因其在肿瘤发生、发展过程中起到重要的调控作用而备受关注。肺癌是迄今发病率及病死率最高的恶性肿瘤。尽管近年来部分肺癌患者的生存期及生活质量有所改善,但其总体预后仍然不佳。因此,积极寻找更加有效的诊断及治疗方法已成为肺癌治疗工作者的严峻任务。了解长链非编码RNA在肺癌发生、发展过程中的作用及其分子机制,将为肺癌的早期诊断及治疗提供新的思路。     

The expression of mesenchymal, neural and haematopoietic stem cell markers in adult hepatocytes proliferating in vitro

BACKGROUND/AIMS: Cultured adult hepatocytes may be stimulated into clonal expansion. We raise the question whether adult hepatocytes proliferating in vitro recapitulate the early process of hepatic development. METHODS: A non-enzymatic method was used to isolate hepatocytes free of contamination with non-parenchymal cells. Hepatocytes were stimulated into proliferation in the presence of mitogens and conditioned media from non-parenchymal cell and hepatocyte culture supernatants. Immunofluorescence methods and PCR analysis were used to demonstrate immunophenotypical characteristics and gene expression profiles similar to those of progenitor cells. RESULTS: Rapid growth occurred during the first 7 days of culture. Cells continued to express hepatic markers (phosphoenolpyruvate carboxykinase, cytokeratin 18, transferrin and dipeptidylpeptidase IV), but the gap junction protein connexin 32 was down-regulated. In the early stage of proliferation, cells started to express biliary and extrahepatic progenitor markers (cytokeratin 19, CD49b, CD49f, nestin, vimentin, Thy1 and c-kit), followed by cytokeratin 7, connexin 43, and neural cell adhesion molecule. Co-expression of the epithelial liver progenitor marker alpha-foetoprotein with either nestin (neural marker) or Thy1 (mesenchymal marker) was also demonstrated. CONCLUSIONS: Mature hepatocytes reveal their potential to regain a spectrum of progenitor markers from different germ layers, suggesting enormous plasticity and differentiation potential of adult liver cells.     

Effect of liver regeneration on malignant hepatic tumors

Liver regeneration after major surgery may activate occult micrometastases and facilitate tumor growth,leading to liver tumor recurrence.Molecular changes during liver regeneration can provide a microenvironment that stimulates intrahepatic tumor propagation through alterations in cellular signaling pathways,where activation and proliferation of mature hepatocytes,hepatic progenitor cells,non-parenchymal liver cells might favor both liver regeneration and tumor growth.This review highlights recent advances of tumor growth and development in the regenerating liver,possible mechanisms and clinical implications.     

肺癌循环肿瘤细胞研究进展

肺癌是引起肿瘤相关死亡的首要原因.循环肿瘤细胞(CTCs)在肺癌的远处转移中起到关键作用.最近研究显示,CTCs水平可以预测肺癌患者的预后和治疗效果.CTCs检测作为一种“液体活检”具有更小的创伤性.CTCs可以及时反映患者的疾病状态,并为肺癌患者提供更好的个体化治疗策略.     

长链非编码RNA-lncRNA2在食管癌中高表达

目的探讨lncRNA2在食管癌中的表达情况,及lncRNA2异常表达作为食管癌的潜在诊断标志物和治疗靶标的可能。方法应用lncRNA表达芯片技术对14对配对的食管癌和癌旁组织进行分析,获得在癌组织和癌旁组织中差异表达>10倍的lncRNA 134个。应用RT-PCR技术在食管癌细胞系进行验证,并分析43对配对的癌及癌旁组织中的表达情况。结果在14个食管癌细胞系中,lncRNA2在10个食管癌细胞系中高表达,而在4个食管癌细胞系中缺失表达。在43对配对的食管癌及癌旁组织中,lncRNA2在26例癌组织中高表达,在癌旁组织中缺失表达或低表达;11例在癌组织中缺失表达或低表达,而在癌旁组织中高表达;另外6例在癌组织和癌旁组织中均缺失表达。lncRNA2在60.47%(26/43)的食管癌组织中高表达,而在25.58%(11/43)的癌旁组织中高表达,差异有统计学意义(P<0.01)。lncRNA2高表达与患者年龄、性别、TNM分期、肿瘤大小、吸烟史、饮酒史、家族史等临床因素无相关性(P均>0.05)。结论lncRNA2在食管癌中表达明显升高,是食管癌潜在的诊断标志物和治疗靶标。     

长链非编码RNA在结直肠癌中的研究现状

近年来研究发现,长链非编码RNA在多种恶性肿瘤的发生发展中发挥重要作用,有望成为新的肿瘤治疗靶点,已成为目前肿瘤研究的热点问题之一。本文对长链非编码RNA的概况及其在结直肠癌预后判断、恶性潜能及诊断中的应用现状做一综述,为结直肠癌的精准治疗提供新的思路与依据。     

长链非编码RNA在结直肠癌中的研究进展

长链非编码RNA（LncRNA）是近十年来肿瘤领域分子机制研究的热点之一,被证实在生物体内对基因的表达具有调控作用,与肿瘤的发生与发展密切相关。结直肠癌是一种严重危害人类健康的恶性肿瘤,研究发现许多LncRNA在结直肠癌中表达失调。异常表达的LncRNA作为关键的调控因子,参与了多种生物学过程,影响肿瘤细胞的增殖和凋亡、侵袭转移及调节肿瘤耐药。研究LncRNA在肠癌中的作用机制可以为结直肠癌临床治疗提供一些新思路。此外,LncRNA还可作为一种潜在的生物标志物用于结直肠癌早期诊断及预后评估。     

长链非编码RNA在结直肠癌中的研究进展

长链非编码RNA(lncRNA)在结直肠癌细胞的表观遗传水平、转录水平和转录后水平调控基因的表达,参与肿瘤细胞的凋亡调控、肿瘤浸润与转移等过程中发挥着促癌或抑癌作用,有希望成为结直肠癌诊断及治疗中的新型分子标记物和治疗靶点。     

长链非编码RNA在药物性肝损伤小鼠肝组织中表达谱的变化

目的：探讨长链非编码RNA（lncRNA）在药物性肝损伤小鼠肝组织中表达谱的变化。方法：利用lncRNA芯片技术检测小鼠正常肝组织和对乙酰氨基酚诱导的药物性肝损伤肝组织中的lncRNA表达谱的变化,通过对原始数据进行预处理达到均一化后,筛选出差异表达的lncRNA并进行分析。结果：与正常肝脏组织比较,其中1.5倍以上变化并且差异有统计学意义（P〈0.05）的lncRNA认为是差异表达的lncRNA。1.5倍以上变化的共68条,1.5倍以上升高的共21条,1.5倍以上降低的共47条;2倍以上升高的共7条,2倍以上降低的共14条;3倍以上升高共2条,3倍以上降低的共5条。结论：药物性肝损伤小鼠肝脏组织与正常小鼠肝脏组织比较,lncRNA表达谱发生了显著变化,提示这些差异性lncRNAs可能参与了药物性肝损伤发生及发展过程。     

The expression and functional mechanism of long non-coding RNA LINC00339 in colorectal cancer

<正>Objective To investigate the expression of long noncoding RNA LINC00339 in colorectal cancer patients and its effect and mechanism on proliferation and apoptosis of colorectal cancer cells. Methods A retrospective analysis     

Aberrant expression of long non-coding RNAs in peripheral blood mononuclear cells response to tuberculosis in children

We aimed to identify long non-coding RNAs (lncRNAs) aberrantly expressed in peripheral blood mononuclear cells (PBMCs) triggered by active tuberculosis (ATB), latent tuberculosis infection (LTBI), and healthy controls (HC). We examined lncRNAs expression in PBMCs isolated from children with ATB and LTBI, and from HC using RNA sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to explore the biological processes and signaling pathways of aberrantly expressed mRNAs. A total of 348 and 205 lncRNAs were differentially expressed in the ATB and LTBI groups, respectively, compared to the HC group. Compared to the LTBI group, 125 lncRNAs were differentially expressed in the ATB group. Compared to the HC group, 2317 mRNAs were differentially expressed in the ATB group, and 1093 mRNAs were differentially expressed in the LTBI group. Compared to the LTBI group, 2328 mRNAs were differentially expressed in the ATB group. The upregulated mRNAs were mainly enriched in neutrophil activation, neutrophil-mediated biological processes, and positive regulation of immune response in tuberculosis (TB), whereas the downregulated mRNAs were enriched in signaling pathways and structural processes, such as the Wnt signaling pathway and rDNA heterochromatin assembly. This is the first study on the differential expression of lncRNAs in PBMCs of children with TB. We identified significant differences in the expression profiles of lncRNAs and mRNAs in the PBMCs of children with ATB, LTBI, and HC, which has important implications for exploring lncRNAs as novel biomarkers for the diagnosis of TB. In addition, further experimental identification and validation of lncRNA roles could help elucidate the underlying mechanisms of Mycobacterium tuberculosis infection in children.     

长链非编码RNA HOTAIR在非小细胞肺癌中的表达及意义

目的探讨长链非编码RNA HOX转录反义RNA(HOTAIR)在非小细胞肺癌(NSCLC)中的表达,及与临床病理及预后的关系。方法收集我院60例NSCLC手术切除标本(包括癌组织及对应的正常肺组织),qRT-PCR检测60例NSCLC中HOTAIR的表达,并分析其与临床病理及预后的关系。结果肺癌组织中的HOTAIR的表达水平(5.18±2.44)显著高于正常肺组织中的表达水平(3.54±1.65)(P0.001)。NSCLC患者肿瘤组织中HOTAIR的表达水平与肿瘤的大小、分化程度及临床分期明显相关(P0.05)。HOTAIR高表达者生存时间明显低于低表达者,差异有显著统计学意义(P0.05)。HOTAIR高表达组和低表达组的中位生存时间分别为46.03和52.9个月。结论 HOTAIR在NSCLC组织中显著高表达,可能成为NSCLC判断预后和治疗的新的分子标记物。     

上皮-间充质转化与非小细胞肺癌EGFR-TKIs获得性耐药关系的研究进展

目前,表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptortyrosine kinase inhibitors,EGFR-TKIs)在非小细胞肺癌中的获得性耐药机制已经成为研究的热点,且针对相应机制治疗EGFR-TKIs获得性耐药非小细胞肺癌的药物也已被研发应用,然而部分获益的患者最终仍然出现了耐药的现象,更多未知的耐药机制仍有待研究探索.近期研究发现,上皮-间充质转化(epithelial to mesenchymal transition,EMT)也与非小细胞肺癌EGFR-TKIs获得性耐药具有—定的相关性,它是一个可诱发肿瘤细胞获得迁移和侵袭能力、促进肿瘤进展的生物学过程.因此,本文主要就EMT的发生机制、EMT与EGFR-TKIs获得性耐药相关关系的研究进展进行详细综述.     

Increased expression of long-noncoding RNA ZFAS1 is associated with epithelial-mesenchymal transition of gastric cancer

LncRNAs play critical roles in gastric cancer (GC). In this study, the expression of fourteen cancer related lncRNAs were investigated in paired tissues of 66 patients with GC, Realtime RT-PCR revealed that ZFAS1 was significantly upregulated. We then examined the expression of ZFAS1 in plasmas derived from 77 GC patients before- and post-operations and 60 healthy individuals, and found that circulating ZFAS1 was also upregulated in GC patients and operation can reduce its presence in plasma. To investigate the potential mechanisms, we compared the expression of ZFAS1 in multiple gastric cell lines and one normal cell line and found that ZFAS1 was up-regulated in GC cell lines. Furthermore, circulating tumor cells (CTC) were simulated by mixing GC cells with peripheral blood. After EpCAM antibody-based cell sorting, we found that the expression of ZFAS1 was positively correlated with EMT property of CTCs. In GC patient tissue samples, we found that Twist was positively correlated with ZFAS1 by immunohistochemical staining. Taken together, our results suggested that ZFAS1 was up-regulated in both tissues and plasmas of GC patients, and may be involved in regulation of EMT in GC progression. Thus, ZFAS1 might serve as a potential diagnostic marker and/or therapeutic target for GC.