脑胶质瘤组织长链非编码RNA FTX、RHPN1-AS1表达与预后的关系

摘要 目的：探讨脑胶质瘤组织长链非编码核糖核酸(LncRNA) FTX、RHPN1-AS1表达与预后的关系。方法：选取我院105例脑胶质瘤患者手术切除的癌组织和癌旁组织（距离肿瘤边缘3~5 cm）。采用实时荧光定量PCR（qRT-PCR）检测组织中LncRNA FTX、RHPN1-AS1表达。分析LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者临床病理特征的关系。K-M法绘制不同LncRNA FTX、RHPN1-AS1表达脑胶质瘤患者术后5年无进展生存期和总生存期曲线。Cox回归分析脑胶质瘤患者预后不良的影响因素。结果：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平高于癌旁组织(P＜0.05)。LncRNA FTX、RHPN1-AS1表达与脑胶质瘤患者卡氏体力状态(KPS)评分和世界卫生组织(WHO)分级相关(P＜0.05)。LncRNA FTX、RHPN1-AS1高表达组无进展生存期和总生存期均短于低表达组(P＜0.05)。KPS评分(HR=2.621,95%CI：1.284～5.348)、WHO分级(HR=2.264,95%CI：1.152～4.449)、LncRNA FTX(HR=1.997,95%CI：1.017～3.922)、LncRNA RHPN1-AS1(HR=2.431,95%CI：1.257～4.701)均是脑胶质瘤患者预后不良的影响因素(P＜0.05)。结论：脑胶质瘤组织中LncRNA FTX、RHPN1-AS1表达水平升高,且二者与KPS评分、WHO分级均是患者预后不良的影响因素,可用于脑胶质瘤患者预后评估。     

脑胶质瘤组织miR-211、miR-374、miR-510表达水平与临床病理特征及预后的关系研究

摘要 目的：探讨脑胶质瘤组织微小RNA（miR）-211、miR-374、miR-510表达水平与临床病理特征及预后的关系。方法：选择2013年8月至2015年8月我院诊治的83例脑胶质瘤患者作为研究对象,选择同期由于脑外伤在我院行内减压术切除的正常脑组织样本31份作为对照样本。采用荧光定量PCR检测miR-211、miR-374、miR-510表达水平,生存分析采用Kaplan-Meier法,应用Cox比例风险回归模型分析预后的影响因素。结果：与正常脑组织相比,脑胶质瘤组织中miR-211、miR-374表达水平明显下降,miR-510表达水平明显升高（P<0.05）。脑胶质瘤组织miR-211、miR-374、miR-510表达均与WHO分级和卡氏功能状态量表(KPS)评分有关（P<0.05）。miR-211、miR-374低表达患者的5年总生存率明显低于高表达患者,miR-510低表达患者的5年总生存率明显高于高表达患者（P<0.05）。WHO分级、KPS评分、miR-211、miR-374和miR-510表达是脑胶质瘤患者预后的影响因素（P<0.05）。结论：脑胶质瘤组织中miR-211和miR-374表达下调,而miR-510表达上调,miR-211、miR-374和miR-510表达均与WHO分级、KPS评分和预后相关,检测miR-211、miR-374和miR-51在脑胶质瘤患者的诊断和治疗中具有一定临床意义。     

B7-H3蛋白在脑胶质瘤中的表达及与疾病发展、预后的关系

为了探讨共刺激分子B7-H7蛋白在脑胶质瘤组织中的表达及与肿瘤发生发展及预后的关系。本研究选取我院病理科收集的100例脑胶质瘤组织作为脑胶质瘤组、40例因外伤等原因进行脑部手术切除的脑组织作为对照组,收集时间为2011年3月至2013年5月,采用免疫组化染色检测两组标本中的B7-H7蛋白表达情况,并分析其与患者临床病理特征、预后的关系。结果显示,脑胶质瘤组织中的B7-H7蛋白阳性表达率(69.00%)显著高于对照组(5.00%)(p0.05);脑胶质瘤组织中的B7-H7蛋白阳性表达与患者肿瘤分级具有显著相关性,随着肿瘤分级增高,阳性表达率增高(p0.05);脑胶质瘤组织中的B7-H7蛋白阳性表达与患者的年龄、性别、病理学类型无关(p0.05);B7-H7蛋白阳性表达的胶质瘤患者的3年生存率(27.87%)低于阴性表达患者(44.83%),但差异无统计学意义(p0.05);B7-H7蛋白阳性表达的胶质瘤患者的生存时间(20.0个月)低于阴性表达患者(28.0个月)(Log Rank(Mantel-Cox)=3.829,p0.05)。本研究表明,B7-H7蛋白在脑胶质瘤组织中表达上调,并且与肿瘤分级、不良预后显著相关。     

神经胶质瘤中PTEN、Ki-67和HIF-1α的表达及临床意义

目的:抑癌基因PTEN、癌基因Ki-67及HIF-1α对多种人类肿瘤的恶性进展均起重要的调控作用。本研究主要探讨PTEN、Ki-67及HIF-1α在人脑胶质瘤中的表达及临床意义,为胶质瘤患者预后的判定、分子病理学的诊断、基因靶向的治疗奠定理论基础。方法:在83例原发性人脑胶质瘤组织样本中,通过免疫组化的方法检测PTEN、Ki-67及HIF-1α的表达情况,并分析其表达相互间及其表达与肿瘤恶性级别之间的相关性。结果:在正常脑组织中,PTEN的表达均为阳性,Ki-67的表达均为阴性,10%(1/10)的样本HIF-1α的表达为阳性。在胶质细胞瘤中,PTEN的表达显著降低(P=0.001),而Ki-67(P0.001)和HIF-1α(P=0.001)的表达明显增高。随肿瘤恶性级别的增高,PTEN的表达呈降低趋势(P0.001),而Ki-67和HIF-1α的表达呈升高趋势(两者P均0.001)。相关性分析表明,PTEN的表达与Ki-67和HIF-1α的表达呈负相关(r值分别为-0.289和-0.304;P值分别为0.008和0.005),Ki-67的表达与HIF-1α的表达呈正相关(r=0.833;P0.001)。结论:胶质瘤组织缺乏抑癌基因PTEN蛋白的表达,而高度表达癌基因Ki-67和HIF-1α。抑癌基因PTEN表达减少或失活,癌基因Ki-67和HIF-1α的过表达对胶质瘤恶性进展可能起到至关重要的作用。PTEN、Ki-67和HIF-1α蛋白的联合检测对胶质瘤恶性程度和预后的判定有十分重要的临床意义。     

基于数据挖掘分析POLR2A基因在脑胶质瘤的表达及意义

目的:基于数据挖掘分析POLR2A基因在低级别脑胶质瘤及正常脑组织中的表达情况,进一步探讨POLR2A基因对低级别脑胶质瘤患者的预后意义。方法:利用Oncomine和GEPIA数据库对POLR2A基因mRNA在正常脑组织和低级别脑胶质瘤组织中的表达进行分析;通过cBioportal分析POLR2A基因在低级别脑胶质瘤组织中的突变情况;利用Onco Lnc数据库对POLR2A基因的表达水平与低级别脑胶质瘤患者生存率做Kaplan-Meier生存分析;使用String-DB数据库探索真核生物表达调控过程中的POLR2A相关蛋白。结果:与正常脑组织相比,低级别脑胶质瘤组织中的POLR2A基因mRNA水平呈显著高表达(P≤0.05);POLR2A基因的表达水平与低级别脑胶质瘤患者的总生存时间无明显相关性;POLR2A基因在低级别脑胶质瘤组织中存在高突变率;真核生物RNA聚合酶POLR2E、POLR2F、POLR2G、POLR2K、POLR2L等与POLR2A有明显的相互作用。结论:数据库中荟萃了POLR2A基因在低级别脑胶质瘤组织中表达的相关信息,证实POLR2A基因在低级别脑胶质瘤组织中呈高表达。     

MAML2基因表达及临床参数与低级别胶质瘤(LGG)患者的诊断及预后价值

脑胶质瘤(Glioma)是最常见的中枢系统恶性肿瘤,MAML2是NOTCH信号通路的共激活因子,通过癌基因组数据库(TCGA)分析验证MAML2基因表达及相关临床参数与低级别胶质瘤(LGG)的诊断及预后价值。从癌基因数据库LGG数据库中下载患者基因表达量数据及患者临床数据,采用统计学方法验证MAML2基因表达差异及临床参数与胶质瘤的诊断与预后关系。在TCGA LGG队列中,发现LGG组织中的MAML2基因较正常组织明显上调(P<0.001),其差异表达可作为低级别胶质瘤的潜在诊断标志物。同时,MAML2低表达组的LGG患者总体生存率低于高表达组(P=0.005 2)。此外,单因素多因素分析提示肿瘤分级,初治后肿瘤再发事件及MAML2低表达是低级别胶质瘤患者的独立危险因素。研究结果表明MAML2基因有可能成为诊断及预测低级别胶质瘤的一个潜在分子标记物。     

Stathmin 在微血管内皮细胞的表达与胶质瘤恶性程度关系

目的:检测Stathmin在正常脑组织及不同级别胶质瘤微血管内皮细胞中的表达情况。方法:利用结合CD105单克隆抗体的免疫磁珠内皮细胞分选系统特异性分选出68例胶质瘤微血管内皮细胞(其中低级别胶质瘤(WHO分级Ⅰ-Ⅱ)24例,高级别胶质瘤(WHO分级Ⅲ-Ⅳ)44例)和20例正常脑组织微血管内皮细胞。应用免疫组化、RT-PCR和Western blot检测Stathmin在胶质瘤微血管内皮细胞和正常脑组织微血管内皮细胞中的表达。结果:免疫组化证实Stathmin在正常脑组织微血管内皮细胞、低级别胶质瘤微血管内皮细胞和高级别胶质瘤微血管内皮细胞的表达百分率分别是20%,66%和95%(P<0.05)。RT-PCR和Western blot法检测显示,Stathmin在胶质瘤微血管内皮细胞中的表达明显增高。低级别胶质瘤组、高级别胶质瘤组分别与正常组比较,均有显著性差异(P<0.01);且低级别胶质瘤组与高级别胶质瘤组比较,有显著性差异(P<0.01),随着胶质瘤恶性程度的增加,Stathmin表达上调,具有统计学意义。结论:Stathmin在脑胶质瘤微血管内皮细胞中表达随肿瘤恶性程度增高而增加,可能为脑胶质瘤的生物治疗提供一个新靶点。     

长链非编码RNA PVT1在肝癌组织中的表达与临床意义

目的:探讨长链非编码RNA PVT1 (lncRNA-PVT1)在肝癌组织中的表达以及在肝癌诊治中的临床意义。方法:采用qRT-PCR法检测肝癌组织和癌旁肝组织中lncRNA-PVT1的表达情况,通过x2检验分析lncRNA-PVT1的表达水平与肝癌患者临床病理指标之间的相关性,采用Kaplan-Meier法绘制患者术后生存曲线,Log-rank检验比较生存率的差异,单因素和多因素分析评估影响肝癌患者预后的独立危险因素。结果:肝癌组织中lncRNA-PVT1的表达水平显著高于癌旁肝组织(P0.05)。肝癌组织lncRNA-PVT1的表达水平与其Edmondson分级、TNM分期、分化程度和是否发生血管转移具有显著相关性(P0.05),而与患者的年龄、性别、血AFP水平、肿瘤直径、肿瘤数目以及是否有肝炎病史无关(P0.05)。lncRNA-PVT1高表达组患者的术后生存率明显低于lncRNA-PVT1低表达组患者,高表达水平的lncRNA-PVT1、Edmondson分级、TNM分期、分化程度和是否发生血管转移均是影响肝癌患者预后的独立危险因素。结论:lncRNA-PVT1在肝癌组织中呈高表达,高表达水平的lncRNA-PVT1与肝癌患者的临床预后不良密切相关,有望成为今后肝癌治疗的新靶点。     

人巨细胞病毒IE1-72蛋白在胶质瘤中的表达及意义

目的:探讨人巨细胞病毒(HCMV)立刻早期基因1-72(IE1-72)蛋白在胶质瘤中的表达水平以及HCMV感染与胶质瘤发生的病因学关系。方法:采用免疫组化方法检测HCMV IE1-72蛋白在125例人脑胶质瘤组织及10例正常人脑组织中的表达,分析其表达水平与胶质瘤临床病理学特征的关系。结果:IE1-72蛋白在胶质瘤组织中的表达水平明显高于正常人脑组织(P=0.000);IE1-72蛋白免疫染色强度随胶质瘤病理级别的升高而明显增强(r=0.310,P=0.000),其在高恶性度胶质瘤中的染色强度明显强于低恶性度胶质瘤(P=0.004);IE1-72蛋白染色强度与胶质瘤患者的年龄存在正相关(r=0.234,P=0.009),而与胶质瘤患者的性别(r=0.038,P=0.675)以及肿瘤部位(r=0.086,P=0.341)无明显相关性。结论:HCMV感染及其蛋白IE1-72表达可能与人脑胶质瘤的发生和发展密切相关,但其确切的致瘤机制尚需进一步研究。     

ABCG2与胶质瘤血管形成及预后的相关研究

目的:研究ABCG2在胶质瘤血管形成过程中与VEGF、VEGFR和CD34的关系,探讨其在血管形成中的作用及对胶质瘤患者生存预后的影响。方法:采用脑胶质瘤的组织芯片技术,分析ABCG2、VEGF和VEGFR(flt-1)在胶质瘤中的表达率,根据CD34阳性的血管计数判定微血管密度(MVD);另用免疫荧光共聚焦检测ABCG2与CD34、VEGF的共表达;用COX回归模型分析ABCG2对胶质瘤患者预后影响。结果:ABCG2、VEGF、VEGFR(flt-1)和CD34阳性表达率随着胶质瘤恶性程度的增加而增高。ABCG2Ⅰ、Ⅱ级之间无统计学差异,其余各级别之间存在统计学差异(P0.05);ABCG2与病理级别呈正相关;ABCG2表达水平与MVD显著相关,γ=0.540,P0.001。ABCG2、VEGF和VEGFR(flt-1)均为阳性表达的肿瘤标本MVD平均值显著高于ABCG2阴性表达者,P0.001。ABCG2与CD34、VEGF共表达于血管壁。COX回归模型证明ABCG2是胶质瘤患者预后的危险因素。结论:ABCG2阳性表达细胞具有向肿瘤血管细胞分化的潜能,对肿瘤血管研究重要意义,且ABCG2表达可作为考察胶质瘤患者预后的重要指标。     

Decreased expression of microRNA-200b is an independent unfavorable prognostic factor for glioma patients

Background and aimAs a member of the microRNA (miR)-200 family, miR-200b has been recognized as one of the fundamental regulators of epithelial–mesenchymal transition, chemosensitivity, cell proliferation, and cell cycle. Especially in glioma, miR-200b targets the CREB1 gene and suppresses the tumor cell growth in vitro. However, its involvement in human glioma has not yet been determined. The aim of this study was to investigate the clinical significance of miR-200b expression in this disease.MethodsmiR-200b expression in 266 pairs of human gliomas and matched nonneoplastic brain tissues was measured by real-time quantitative RT-PCR assay.ResultsCompared with nonneoplastic brain tissues, the expression level of miR-200b was significantly decreased in glioma tissues (tumor vs. normal: 2.87 ± 2.05 vs. 8.78 ± 2.50, P < 0.001). Of 266 patients with gliomas, 166 (62.41%) were in low miR-200b expression group. In addition, we found that the glioma tissues from high-grade tumors (grade III and IV) had much lower miR-200b expression than glioma tissues from low grade tumors (grade I and II). Moreover, the expression level of miR-200b was positively correlated with Karnofsky performance status (KPS) scores of glioma tissues. The results of a 60-month follow-up in 266 glioma patients further demonstrated that lower miR-200b expression was correlated with worse progression-free survival and overall survival in the patients with grade III and IV gliomas. Both univariate and multivariate analyses revealed that miR-200b was an independent prognostic indicator for glioma.ConclusionThese findings prove that the decreased expression of miR-200b may be associated with malignant tumor progression and poor prognosis in patients with gliomas, suggesting the potential role of miR-200b in glioma management. miR-200b may be a novel and valuable signature for predicting the clinical outcome of patients with gliomas.     

Long Non-coding RNA HOXA10-AS Promotes Invasion and Migration of Hepatocellular Carcinoma Cells

Some studies have showed that long non-coding RNA (lncRNA) HOXA10-AS acts as an oncogene and regulates the invasion and metastasis of tumor cells. However, its mechanism in the invasion and migration of hepatocellular carcinoma (HCC) cells is unclear. The purpose of this study was to analyze the expression of HOXA10-AS in HCC tissues and its clinical significance, detect the influence of HOXA10-AS on the invasion and migration of HCC cells, and explore the mechanism of HOXA10-AS in promoting the invasion and migration of HCC cells. The results of quantitative real-time PCR (qRT-PCR) showed that the expression of HOXA10-AS was significantly upregulated in HCC tissues compared with the adjacent non-HCC tissues. Age and gender did not show significant correlation with HOXA10-AS expression, while tumor size, lymphatic metastasis and distant metastasis showed significant correlation with HOXA10-AS expression. Meanwhile, the expression of HOXA10-AS in HCC cells was higher than that in normal liver cells. After interfering with HOXA10-AS in HCC cell lines HepG2 and QGY7701, Transwell invasion and scratch experiments showed that the invasion and migration ability of HOXA10-AS cells in the HOXA10-AS group was significantly lower than that in the control group. Western blotting results showed that the expression levels of vimentin and N-cadherin were significantly lower than those of the control group, while the E-cadherin expression was significantly increased. The TGFβ1/Smads signaling pathway was inhibited after HOXA10-AS interference. In summary, HOXA10-AS promotes the invasion and migration of HCC cells by the TGFβ1/Smads signaling pathway.     

Long noncoding RNA FOXD2-AS1 promotes glioma malignancy and tumorigenesis via targeting miR-185-5p/CCND2 axis

Glioma is the most aggressive malignant tumor in the adult central nervous system. Abnormal long noncoding RNA (lncRNA) FOXD2-AS1 expression was associated with tumor development. However, the possible role of FOXD2-AS1 in the progression of glioma is not known. In the present study, we used in vitro and in vivo assays to investigate the effect of abnormal expression of FOXD2-AS1 on glioma progression and to explore the mechanisms. FOXD2-AS1 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of FOXD2-AS1 was correlated with poor prognosis of glioma. Downregulation of FOXD2-AS1 decreased cell proliferation, migration, invasion, stemness, and epithelial-mesenchymal transition (EMT) in glioma cells and inhibited tumor growth in transplanted tumor. We also revealed that FOXD2-AS1 was mainly located in cytoplasm and microRNA (miR)-185-5p both targeted FOXD2-AS1 and CCND2 messenger RNA (mRNA) 3′-untranslated region (3′-UTR). miR-185-5p was downregulated in glioma tissue, cells, and sphere subpopulation. Downregulation of miR-185-5p was closely correlated with poor prognosis of glioma patients. In addition, miR-185-5p mimics decreased cell proliferation, migration, invasion, stemness, and EMT in glioma cells. CCND2 was upregulated in glioma tissue, cells, and sphere subpopulation. Upregulation of CCND2 was closely correlated with poor prognosis of glioma patients. CCND2 knockdown decreased cell proliferation, migration, invasion, and EMT in glioma cells. In glioma tissues, CCND2 expression was negatively associated with miR-185-5p, but positively correlated with FOXD2-AS1. FOXD2-AS1 knockdown and miR-185-5p mimics decreased CCND2 expression. Inhibition of miR-185-5p suppressed FOXD2-AS1 knockdown-induced decrease of CCND2 expression. Overexpression of CCND2 suppressed FOXD2-AS1 knockdown-induced inhibition of glioma malignancy. Taken together, our findings highlight the FOXD2-AS1/miR-185-5p/CCND2 axis in the glioma development.     

LncRNA DLX6-AS1 promotes tumor proliferation and metastasis in osteosarcoma through modulating miR-641/HOXA9 signaling pathway

Osteosarcoma (OS) is the most common primary malignant bone tumor. Recently, increasing evidence has shown that the long noncoding RNA (lncRNA) DLX6-AS1 (distal-less homeobox 6 antisense 1) plays significant roles in various types of cancers. However, the functions and underlying mechanisms of DLX6-AS1 have not been explored in OS yet. In this study, we assessed the expression of DLX6-AS1 in OS tissues and cell lines and explored the underlying molecular mechanisms. DLX6-AS1 was found to be significantly upregulated in OS tissues and OS cell lines. High expression of DLX6-AS1 was significantly correlated with advanced TNM stage, high tumor grade, and distant metastasis of patients with OS. Knockdown of DLX6-AS1 suppressed OS cell proliferation, invasion, and migration, and induced cell apoptosis. Knockdown of DLX6-AS1 also suppressed in vivo tumor growth. Bioinformatics and luciferase assay analysis showed that DLX6-AS1 functioned as a competing endogenous RNA (ceRNA) to negatively regulate miR-641 expression. Furthermore, miR-641 was found to target the 3′ untranslated region of homeobox protein Hox-A9 (HOXA9) and suppressed the expression of HOXA9. Mechanistic studies showed that DLX6-AS1 regulated OS cell proliferation, invasion, and migration via regulating HOXA9 by acting as a ceRNA for miR-641. Our results suggested that DLX6-AS1 functions as a ceRNA by targeting miR-641/HOXA9 signal pathway to suppress OS cell proliferation and metastasis. Our study may provide novel insights into understanding pathogenesis and development of OS.     

Comprehensive analysis of the long noncoding RNA HOXA11-AS gene interaction regulatory network in NSCLC cells

Background

Long noncoding RNAs (lncRNAs) are related to different biological processes in non-small cell lung cancer (NSCLC). However, the possible molecular mechanisms underlying the effects of the long noncoding RNA HOXA11-AS (HOXA11 antisense RNA) in NSCLC are unknown.

Methods

HOXA11-AS was knocked down in the NSCLC A549 cell line and a high throughput microarray assay was applied to detect changes in the gene profiles of the A549 cells. Bioinformatics analyses (gene ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) were performed to investigate the potential pathways and networks of the differentially expressed genes. The molecular signatures database (MSigDB) was used to display the expression profiles of these differentially expressed genes. Furthermore, the relationships between the HOXA11-AS, de-regulated genes and clinical NSCLC parameters were verified by using NSCLC patient information from The Cancer Genome Atlas (TCGA) database. In addition, the relationship between HOXA11-AS expression and clinical diagnostic value was analyzed by receiver operating characteristic (ROC) curve.

Results

Among the differentially expressed genes, 277 and 80 genes were upregulated and downregulated in NSCLC, respectively (fold change ≥2.0, P < 0.05 and false discovery rate (FDR) < 0.05). According to the degree of the fold change, six upregulated and three downregulated genes were selected for further investigation. Only four genes (RSPO3, ADAMTS8, DMBT1, and DOCK8) were reported to be related with the development or progression of NSCLC based on a PubMed search. Among all possible pathways, three pathways (the PI3K-Akt, TGF-beta and Hippo signaling pathways) were the most likely to be involved in NSCLC development and progression. Furthermore, we found that HOXA11-AS was highly expressed in both lung adenocarcinoma and squamous cell carcinoma based on TCGA database. The ROC curve showed that the area under curve (AUC) of HOXA11-AS was 0.727 (95% CI 0.663–0.790) for lung adenocarcinoma and 0.933 (95% CI 0.906–0.960) for squamous cell carcinoma patients. Additionally, the original data from TCGA verified that ADAMTS8, DMBT1 and DOCK8 were downregulated in both lung adenocarcinoma and squamous cell carcinoma, whereas RSPO3 expression was upregulated in lung adenocarcinoma and downregulated in lung squamous cell carcinoma. For the other five genes (STMN2, SPINK6, TUSC3, LOC100128054, and C8orf22), we found that STMN2, TUSC3 and C8orf22 were upregulated in squamous cell carcinoma and that STMN2 and USC3 were upregulated in lung adenocarcinoma. Furthermore, we compared the correlation between HOXA11-AS and de-regulated genes in NSCLC based on TCGA. The results showed that the HOXA11-AS expression was negatively correlated with DOCK8 in squamous cell carcinoma (r = ?0.124, P = 0.048) and lung adenocarcinoma (r = ?0.176, P = 0.005). In addition, RSPO3, ADAMTS8 and DOCK8 were related to overall survival and disease-free survival (all P < 0.05) of lung adenocarcinoma patients in TCGA.

Conclusions

Our results showed that the gene profiles were significantly changed after HOXA11-AS knock-down in NSCLC cells. We speculated that HOXA11-AS may play an important role in NSCLC development and progression by regulating the expression of various pathways and genes, especially DOCK8 and TGF-beta pathway. However, the exact mechanism should be verified by functional experiments.

     

Long noncoding RNA FLVCR1-AS1 aggravates biological behaviors of glioma cells via targeting miR-4731-5p/E2F2 axis

Long noncoding RNAs (lncRNAs) display essential roles in cancer progression. FLVCR1-AS1 is a rarely investigated lncRNAs involved in various human cancers, such as hepatocellular carcinoma and lung cancer. However, its function in glioma has not been clarified. In our study, we found that FLVCR1-AS1 was highly expressed in glioma tissues and cell lines. And upregulation of FLVCR1-AS1 predicted poor prognosis in patients with glioma. Moreover, FLVCR1-AS1 knockdown inhibited proliferation, migration and invasion of glioma cells. Through bioinformatics analysis, we identified that FLVCR1-AS1 was a sponge for miR-4731-5p to upregulate E2F2 expression. Moreover, rescue assays indicated that FLVCR1-AS1 modulated E2F2 expression to participate in glioma progression. Altogether, our research demonstrates that the FLVCR1-AS1/miR-4731-5p/E2F2 axis is a novel signaling in glioma and may be a potential target for tumor therapy.     

Long noncoding RNA FOXD2-AS1 promotes glioma cell cycle progression and proliferation through the FOXD2-AS1/miR-31/CDK1 pathway

Long noncoding RNAs (lncRNAs) are vital mediators involved in cancer progression. Previous studies confirmed that FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is upregulated in tumor diseases. The potential influence of FOXD2-AS1 in glioma progression, however, remains unknown. In this paper, FOXD2-AS1 was found to be upregulated in glioma tissues. Its level was linked with glioma stage. Moreover, glioma patients expressing high level of FOXD2-AS1 suffered worse prognosis. Biological functions of FOXD2-AS1 in glioma cells were analyzed through integrative bioinformatics and TCGA RNA sequencing data analysis. Pathway enrichment analysis uncovered that FOXD2-AS1 was mainly linked with cell cycle regulation in both low-grade glioma and glioblastoma. Further experiments demonstrated that silence of FOXD2-AS1 inhibited proliferation, arrested cell cycle and downregulated cyclin-dependent kinase 1 (CDK1) in human glioma cells. Dual-luciferase reporter assay confirmed that FOXD2-AS1 upregulated CDK1 by sponging miR-31. Rescue assays were performed and confirmed the regulatory loop FOXD2-AS1/miR-31/CDK1 in glioma. Collectively, our results indicated that the FOXD2-AS1/miR-31/CDK1 axis influenced glioma progression, providing a potential new target for glioma patients.