Identification of functional lncRNAs in gastric cancer by integrative analysis of GEO and TCGA data

Gastric cancer (GC) is a prevalent malignant cancer of digestive system, identification of novel diagnostic and prognostic biomarkers for GC is urgently demanded. The aim of this study was to determine potential long noncoding RNAs (lncRNAs) associated with the pathogenesis and prognosis of GC. Raw noncoding RNA microarray data (GSE53137, GSE70880, and GSE99417) was downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes between GC and adjacent normal gastric tissue samples were screened by an integrated analysis of multiple gene expression profile after gene reannotation and batch normalization. Differentially expressed genes were further confirmed by The Cancer Genome Atlas (TCGA) database. Competing endogenous RNA (ceRNA) network, Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway, survival analysis were extensively applied to identify hub lncRNAs and discover potential biomarkers related to diagnosis and prognosis of GC. In total of 246 integrated differential genes including 15 lncRNAs and 241 messenger RNAs (mRNAs) were obtained after intersections of differential genes between GEO and TCGA database. ceRNA network comprised of three lncRNAs (UCA1, HOTTIP, and HMGA1P4), 26 microRNAs (miRNAs) and 72 mRNAs. Functional analysis revealed that three lncRNAs were mainly dominated in cell cycle and cellular senescence. Survival analysis showed that HMGA1P4 was statistically related to the overall survival rate. For the first time, we identified that HMGA1P4, a target of miR-301b/miR-508, is involved in cell cycle and senescence process by regulating CCNA2 in GC. Finally, the expression levels of three lncRNAs were validated to be upregulated in GC tissues. Thus, three lncRNAs including UCA1, HOTTIP, and HMGA1P4 may contribute to GC development and their potential functions might be associated with the prognosis of GC.     

Crosstalk between lncRNAs in the apoptotic pathway and therapeutic targets in cancer

The assertion that a significant portion of the mammalian genome has not been translated and that non-coding RNA accounts for over half of polyadenylate RNA have received much attention. In recent years, increasing evidence proposes non-coding RNAs (ncRNAs) as new regulators of various cellular processes, including cancer progression and nerve damage. Apoptosis is a type of programmed cell death critical for homeostasis and tissue development. Cancer cells often have inhibited apoptotic pathways. It has recently been demonstrated that up/down-regulation of various lncRNAs in certain types of tumors shapes cancer cells' response to apoptotic stimuli. This review discusses the most recent studies on lncRNAs and apoptosis in healthy and cancer cells. In addition, the role of lncRNAs as novel targets for cancer therapy is reviewed here. Finally, since it has been shown that lncRNA expression is associated with specific types of cancer, the potential for using lncRNAs as biomarkers is also discussed.     

Urinary exosomal long noncoding RNAs serve as biomarkers for early detection of non-small cell lung cancer

Objective: Increasing the efficiency of early diagnosis using noninvasive biomarkers is crucial for enhancing the survival rate of lung cancer patients. We explore the differential expression of non-small cell lung cancer (NSCLC)-related long noncoding RNAs (lncRNAs) in urinary exosomes in NSCLC patients and normal controls to diagnose lung cancer.Methods: A differential expression analysis between NSCLC patients and healthy controls was performed using microarrays. Gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to predict potential functions of lncRNAs in NSCLC. quantitative real-time PCR (QT-PCR) was used to verify microarray results.Results: A total of 640 lncRNAs (70 up- and 570 down-regulated) were differentially expressed in NSCLC patients in comparison to healthy controls. Six lncRNAs were detected by QT-PCR. GO term and KEGG pathway analyses showed that differential lncRNAs were enriched in cellular component organization or biogenesis, as well as other biological processes and signaling pathways, such as the PI3K-AKT, FOXO, p53, and fatty acid biosynthesis.Conclusions: The differential lncRNAs in urinary exosomes are potential diagnostic biomarkers of NSCLC. The lncRNAs enriched in specific pathways may be associated with tumor cell proliferation, tumor cell apoptosis, and the cell cycle involved in the pathogenesis of NSCLC.     

长链非编码RNA相关表观遗传修饰在癌症中的进展*

长链非编码RNA(lncRNA)是一类转录本长度大于200 nt的RNA分子,编码蛋白质的功能有限,但其功能多样且复杂。已有研究报道lncRNA与肿瘤的发展进程密切相关,lncRNA可以通过不同方式参与细胞内生物学进程的调控,是潜在的癌症调节因子,其中,调节表观遗传修饰水平是其影响癌症进程的主要手段;癌症发病过程中细胞内存在着不同程度的表观遗传修饰,其主要为包括甲基化、乙酰化、磷酸化、糖基化、泛素化等修饰方式在内的DNA修饰、RNA修饰以及蛋白质的翻译后修饰,在癌症的不同阶段其修饰的异常程度不同,从而影响肿瘤发生的生物学进程。研究表明,lncRNA可以通过自身修饰或参与其他生物大分子的表观遗传修饰进程参与癌症的发生发展。因此,回顾了lncRNA所参与的表观遗传修饰形式和lncRNA在表观遗传修饰方面所起到的作用,并概述了lncRNA通过影响表观遗传修饰水平从而调控癌症进程的方法。旨在总结癌症细胞内表观遗传修饰方面所涉及lncRNA的研究进展,为癌症诊断和治疗提供潜在的靶标和生物学标志物。     

循环长链非编码RNA作为生物标志物在肿瘤分子诊断中的应用

长链非编码RNA(Long noncoding RNA,lncRNA)被发现广泛参与基因表达、表观遗传调控和X染色体失活等重要生命过程,还与肿瘤发生和发展密切相关。lncRNA可能以微泡、外泌体或蛋白质复合物形式进入人体循环系统中,形成循环lncRNA稳定而广泛存在于血液、尿液等体液中。文中简要回顾了近来关于循环lncRNA的来源,以及作为生物标志物的检测方法,着重总结分析了循环lncRNA作为潜在肿瘤生物标志物在肺癌、乳腺癌、胃癌、肝癌、结直肠癌和前列腺癌等常见恶性肿瘤中的早期诊断价值。与传统生物标志物相比,循环lncRNA具有作为新型生物标志物的独特优势和临床应用价值。     

A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer

The early detection of lung cancer is a major clinical challenge. Long noncoding RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly released from primary tumors or the circulating cancer cells might provide cell-free cancer biomarkers. The objective of this study was to investigate whether the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By using droplet digital polymerase chain reaction, we determined the diagnostic performance of 26 lung cancer–associated lncRNAs in plasma of a development cohort of 63 lung cancer patients and 33 cancer-free individuals, and a validation cohort of 39 lung cancer patients and 28 controls. In the development cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and RMRP) displayed a considerably high plasma level in lung cancer patients vs. cancer-free controls (all P?<?.001). Combined use of the plasma lncRNAs as a biomarker signature produced 84.13% sensitivity and 87.88% specificity for diagnosis of lung cancer, independent of stage and histological type of lung tumor, and patients' age and sex (all P?>?.05). The diagnostic value of the plasma lncRNA signature for lung cancer early detection was confirmed in the validation cohort. The plasma lncRNA signature may provide a potential blood-based assay for diagnosing lung cancer at the early stage. Nevertheless, a prospective study is warranted to validate its clinical value.     

microRNAs and long non‐coding RNAs as biomarkers for polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non‐coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.     

LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine

Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30–35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.     

The potential role of exosomes derived from ovarian cancer cells for diagnostic and therapeutic approaches

Most patients with ovarian cancer (OC) are diagnosed at the advanced stages due to the absence of appropriate early diagnostic markers. Thus, OC is a gynecological disease with a low-survival rate. Exosomes are extracellular vesicles that are widely being considered as mediators for the noninvasive diagnosis of OC. Exosomes are expected to aid in the effective diagnosis of OC because they carry components, such as RNAs, proteins, and lipids, the compositions of which vary depending on the pathological characteristics of the patient. In this review, we document the methods that have been developed to detect exosomes and their components in OC. We also assess the potential biomarkers contained in exosomes that could be clinically useful, such as proteins, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and phospholipids. Moreover, we described the role played by exosomes in the tumor microenvironment and in OC angiogenesis, migration, and tumor growth. Various types of cells in the tumor microenvironment, including macrophages, fibroblasts, and mesenchymal stem cells (MSCs), interact directly with exosomes and promote or inhibit the progression of OC. Therefore, we summarize the studies that have suggested a therapeutic approach to OC using exosomes. Collectively, understanding the mechanism of exosome-based OC progression would broaden our knowledge regarding the diagnosis and therapy of OC.     

Long noncoding RNAs expression in gastric cancer

Long noncoding RNAs (lncRNAs) have been involved in the pathogenesis of several human cancers including gastric cancer. In the current study, we selected five lncRNAs namely NEAT1, TUG1, PANDA, UCA1, and GHET1 to assess their expressions in gastric cancer samples compared with adjacent noncancerous tissues (ANCTs) from the same patients. Some previous reports have shown contribution of these lncRNAs in gastric cancer. However, we aimed to explore their associations with patients’ clinicopathological data and their potential as diagnostic biomarkers. Significant associations were found between site of primary tumor and relative expression of all lncRNAs in cancer samples compared with ANCTs. Besides, GHET1 relative expression was associated with lymph node status. The diagnostic power of GHET1 was higher from other lncRNAs. Combination of GHET1, TUG1, UCA1, and PANDA increased the diagnostic power and significance (AUC = 0.8; P < 0.0001). The current study supports participation of lncRNAs in the pathogenesis of gastric cancer and highlights their potential as diagnostic biomarkers.     

Leukemia-derived exosomes: Bringing oncogenic signals to blood cells

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.