Long noncoding RNA profiles of adrenocortical cancer can be used to predict recurrence

2015 ◽  
Vol 22 (1) ◽  
pp. 99-109 ◽  
Author(s):  
A R Glover ◽  
J T Zhao ◽  
J C Ip ◽  
J C Lee ◽  
B G Robinson ◽  
...  

Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence following surgical resection. Long noncoding RNAs (lncRNAs) play an important role in cancer development. Pathogenesis of adrenal tumours have been characterised by mRNA, microRNA and methylation expression signatures, but it is unknown if this extends to lncRNAs. This study describes lncRNA expression signatures in ACC, adrenal cortical adenoma (ACA) and normal adrenal cortex (NAC) and presents lncRNAs associated with ACC recurrence to identify novel prognostic and therapeutic targets. RNA was extracted from freshly frozen tissue with confirmation of diagnosis by histopathology. Focused lncRNA and mRNA transcriptome analysis was performed using the ArrayStar Human LncRNA V3.0 microarray. Differentially expressed lncRNAs were validated using quantitative reverse transcriptase-PCR and correlated with clinical outcomes. Microarray of 21 samples (ten ACCs, five ACAs and six NACs) showed distinct patterns of lncRNA expression between each group. A total of 956 lncRNAs were differentially expressed between ACC and NAC, including known carcinogenesis-related lncRNAs such as H19, GAS5, MALAT1 and PRINS (P≤0.05); 85 lncRNAs were differentially expressed between ACC and ACA (P≤0.05). Hierarchical clustering and heat mapping showed ACC samples correctly grouped compared with NAC and ACA. Sixty-six differentially expressed lncRNAs were found to be associated with ACC recurrence (P≤0.05), one of which, PRINS, was validated in a group of 20 ACCs and also found to be associated with metastatic disease on presentation. The pathogenesis of adrenal tumours extends to lncRNA dysregulation and low expression of the lncRNA PRINS is associated with ACC recurrence.

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Wei Zhang ◽  
Lin Wang ◽  
Fang Zheng ◽  
Ruhai Zou ◽  
Changqing Xie ◽  
...  

Long noncoding RNAs (lncRNAs) have recently been found to play important roles in various cancer types. The elucidation of genome-wide lncRNA expression patterns in metastatic nasopharyngeal carcinoma (NPC) could reveal novel mechanisms underlying NPC carcinogenesis and progression. In this study, lncRNA expression profiling was performed on metastatic and primary NPC tumors, and the differentially expressed lncRNAs between these samples were identified. A total of 33,045 lncRNA probes were generated for our microarray based on authoritative data sources, including RefSeq, UCSC Knowngenes, Ensembl, and related literature. Using these probes, 8,088 lncRNAs were found to be significantly differentially expressed (≥2-fold). To identify the prognostic value of these differentially expressed lncRNAs, four lncRNAs (LOC84740, ENST00000498296, AL359062, and ENST00000438550) were selected; their expression levels were measured in an independent panel of 106 primary NPC samples via QPCR. Among these lncRNAs, ENST00000438550 expression was demonstrated to be significantly correlated with NPC disease progression. A survival analysis showed that a high expression level of ENST00000438550 was an independent indicator of disease progression in NPC patients (P=0.01). In summary, this study may provide novel diagnostic and prognostic biomarkers for NPC, as well as a novel understanding of the mechanism underlying NPC metastasis and potential targets for future treatment.


2019 ◽  
Vol 89 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Hao Liu ◽  
Yiping Huang ◽  
Yingying Zhang ◽  
Yineng Han ◽  
Yixin Zhang ◽  
...  

ABSTRACT Objectives: To investigate the long noncoding RNA (lncRNA) expression profile of cementoblasts under compressive force. Materials and Methods: Mouse cementoblasts were exposed to compression (1.5 g/cm2) for 8 hours. RNA sequencing (RNA-seq) was performed to compare the transcriptomes of the compressed and control cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate five of the differentially expressed lncRNAs of interest. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also performed. Results: A total of 70 lncRNAs and 521 mRNAs were differentially regulated in cementoblasts subjected to compressive loading. Among the differentially expressed lncRNAs, 57 were upregulated and 13 downregulated. The expression levels of the five selected lncRNAs (Prkcz2, Hklos, Trp53cor1, Gdap10, and Ak312-ps) were validated by qRT-PCR and consistent with the RNA-seq results. GO functional annotation demonstrated upregulation of genes associated with cellular response to hypoxia and apoptotic processes during compressive loading. KEGG analysis identified the crucial pathways involving the hypoxia-inducing factor-1α, forkhead box O, and mammalian target of rapamycin signaling pathways. Conclusions: Mechanical compression changes the lncRNA expression profile of cementoblasts, providing important references for further investigation into the role and regulation of lncRNAs in compressed cementoblasts and root resorption during orthodontic treatment.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Krishna K. Singh ◽  
Pratiek N. Matkar ◽  
Adrian Quan ◽  
Laura-Eve Mantella ◽  
Hwee Teoh ◽  
...  

Objective. To evaluate the relationship between TGFβsignaling and endothelial lncRNA expression.Methods.Human umbilical vein endothelial cell (HUVECs) lncRNAs and mRNAs were profiled with the Arraystar Human lncRNA Expression Microarray V3.0 after 24 hours of exposure to TGFβ1 (10 ng/mL).Results. Of the 30,584 lncRNAs screened, 2,051 were significantly upregulated and 2,393 were appreciably downregulated (P<0.05) in response to TGFβ. In the same HUVEC samples, 2,148 of the 26,106 mRNAs screened were upregulated and 1,290 were downregulated. Of these 2,051 differentially expressed upregulated lncRNAs, MALAT1, which is known to be induced by TGFβin endothelial cells, was the most (~220-fold) upregulated lncRNA. Bioinformatics analyses indicated that the differentially expressed upregulated mRNAs are primarily enriched in hippo signaling, Wnt signaling, focal adhesion, neuroactive ligand-receptor interaction, and pathways in cancer. The most downregulated are notably involved in olfactory transduction, PI3-Akt signaling, Ras signaling, neuroactive ligand-receptor interaction, and apoptosis.Conclusions.This is the first lncRNA and mRNA transcriptome profile of TGFβ-mediated changes in human endothelial cells. These observations may reveal potential new targets of TGFβin endothelial cells and novel therapeutic avenues for cardiovascular disease-associated endothelial dysfunction.


2021 ◽  
Author(s):  
Songhao Yang ◽  
Xiancai Du ◽  
Chan Wang ◽  
Tingrui Zhang ◽  
Shimei Xu ◽  
...  

Abstract Background: Cystic echinococcosis (CE) is a severe and neglected zoonotic disease, which is caused by Echinococcus granulosus sensu lato and poses health and socioeconomic hazards. RNA molecules play important roles in genetic coding, translation, regulation, and gene expression and are classified into noncoding RNAs, such as long noncoding RNAs (lncRNAs), miRNAs, and circular RNAs (circRNAs), and coding RNAs (mRNAs) based on whether they encode proteins.Methods: Peripheral blood serum from E. granulosus-infected and uninfected female BALB/c mice was used to measure IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α levels using the cytometric bead array mouse Th1/Th2/Th17 cytokine kit. mRNA, lncRNA, miRNA, and circRNA profiles were analyzed in spleen CD4+ T cells from the two groups of mice using high-throughput sequencing.Results: The results showed that the levels of serum IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α were significantly higher in the CE mice than in the control group (P < 0. 01). A total of 1,758 known mRNAs, 37 miRNAs, 175 lncRNAs, and 22 circRNAs were differentially expressed between infected and uninfected mice (|fold change| ≥ 0.585, P < 0.05). These differentially expressed molecules were closely related to the JAK/STAT, mitogen-activated protein kinase, p53, and PI3K/Akt signaling pathways, cell cycle, and metabolic pathways.Conclusions: E. granulosus infection caused significant increases in the IFN-γ, IL-2, IL-4, IL-6, IL-10, IL-17A, and TNF-α levels in the peripheral blood of mice, as well as significant changes in the expression levels of a variety of coding and noncoding RNAs. A further study of these trends and pathways may help clarify the pathogenesis of CE and provide new insights into the prevention and treatment of this infection.


Epigenomics ◽  
2020 ◽  
Vol 12 (15) ◽  
pp. 1303-1315
Author(s):  
Weibo Du ◽  
Wenbiao Chen ◽  
Zheyue Shu ◽  
Dairong Xiang ◽  
Kefan Bi ◽  
...  

Aim: This study aimed to identify long noncoding RNAs (lncRNAs) with potential to be prognostic biomarkers of hepatocellular carcinoma (HCC) by analyzing copy number alterations (CNAs). Methods: RNA Sequencing data of 369 HCC patients was downloaded from The Cancer Genome Atlas database and analyzed with a series of systematic bioinformatics methods. Results: LncRNA-CNA association analysis revealed that many lncRNAs were located in sites frequently amplified or deleted. Three upregulated lncRNAs (LINC00689, SNHG20 and MAFG-AS1) with copy amplification and one downregulated lncRNA TMEM220-AS1 with copy deletion were associated with poor prognosis of HCC. Conclusion: This study reveals that differentially expressed lncRNAs correlate with CNAs in HCC. Moreover, the differentially expressed lncRNAs and their copy amplification/deletions could be promising prognostic biomarkers of HCC.


2020 ◽  
Author(s):  
Liang Shao ◽  
Yanan Ming ◽  
Zhaoming Zhou

Abstract BackgroundsGastric cancer (GC) is one of the most malignant epithelial tumors. The incidence of GC varies worldwide, and nearly half of the cases occur in Asian countries, especially in Japan and China. GC is the 3rd leading cause of cancer-related deaths in the world, and current prognosis of advanced GC remains dismal despite improvements in diagnosis and therapy. Our current study aimed to identify significant long noncoding RNAs with the prognostic potential and preliminarily to investigate the underlying mechanisms the identified long noncoding RNAs.MethodsWe retrieved articles reporting human LncRNA microarray in GC patients and pooled eligible studies for meta-analysis. GEO2R and Qigen’s IPA analysis was utilized for searching potential interacted molecules with differentially expressed LncRNA in GC. The expression of eligible LncRNA and molecules in GC were validated in public GC dataset by GEPIA website. And Kaplan Meier plots was employed to analyze the correlation between target molecules and prognosis of GC.ResultsThis study identified a variety of reports to investigate the expression of lncRNAs in GC development using high-throughput lncRNA detection. Eight of them were further verified with significant expression in GC tissues by using Gene Expression Profiling Interactive Analysis (GEPIA). Next, the molecular interactions with eight lncRNAs were further identified by using Qiagen’s IPA system. Simultaneously, differentially expressed genes (DEGs) of GC were also identified via the GEO2R online tool and datasets (GSE54129, GSE19826, and GSE79973). Finally, through Venn diagram analysis, our study found that IGF2BP3 and FOLR1 have strong relationship with lncRNAs H19 and PVT1 respectively in the background of stomach cancer. The expression of IGF2BP3 and FOLR1 in GC was further revealed to be correlate to a worsening prognosis for GC patients by Kaplan Meier plots. IGF2BP3 promotes the expression of H19 and PEG10, the down-regulation of which might improve the GC prognosis. FOLR1 is a crucial component of cell metabolism and DNA synthesis/repair required for cancer cell division. Currently, there is no evidence to report IGF2BP3 and FOLR1 to correlate to GC prognosis.ConclusionIn summary, using an integrated bioinformatic approach we identified eight lncRNAs with prognostic potential in GC patients and further revealed two axes - H19-IGF2BP3 and PVT1-FOLR1 – that might interpret the underlying mechanism involving in prognosis of GC and provide new insights into the etiology and management of GC patients.


Biology ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 232
Author(s):  
Weiran Zheng ◽  
Haichao Hu ◽  
Qisen Lu ◽  
Peng Jin ◽  
Linna Cai ◽  
...  

Recent studies have shown that a large number of long noncoding RNAs (lncRNAs) can regulate various biological processes in animals and plants. Although lncRNAs have been identified in many plants, they have not been reported in the model plant Nicotiana benthamiana. Particularly, the role of lncRNAs in plant virus infection remains unknown. In this study, we identified lncRNAs in N. benthamiana response to Chinese wheat mosaic virus (CWMV) infection by RNA sequencing. A total of 1175 lncRNAs, including 65 differentially expressed lncRNAs, were identified during CWMV infection. We then analyzed the functions of some of these differentially expressed lncRNAs. Interestingly, one differentially expressed lncRNA, XLOC_006393, was found to participate in CWMV infection as a precursor to microRNAs in N. benthamiana. These results suggest that lncRNAs play an important role in the regulatory network of N. benthamiana in response to CWMV infection.


Oncogene ◽  
2021 ◽  
Vol 40 (17) ◽  
pp. 3164-3179
Author(s):  
Yang Liu ◽  
Tianchi Tang ◽  
Xiaosheng Yang ◽  
Peng Qin ◽  
Pusen Wang ◽  
...  

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most fatal malignancies and rapidly progressive diseases. Exosomes and long noncoding RNAs (lncRNAs) are emerging as vital mediators in tumor cells and their microenvironment. However, the detailed roles and mechanisms of exosomal lncRNAs in PDAC progression remain unknown. Here, we aimed to clarify the clinical significance and mechanisms of exosomal lncRNA 01133 (LINC01133) in PDAC. We analyzed the expression of LINC01133 in PDAC and found that exosomal LINC01133 expression was high and positively correlated with higher TNM stage and poor overall survival rate of PDAC patients. Further research demonstrated that Periostin could increase exosome secretion and then enhance LINC01133 expression. In addition, Periostin increased p-EGFR, p-Erk, and c-myc expression, and c-myc could bind to the LINC01133 promoter region. These findings suggested that LINC01133 can be regulated by Periostin via EGFR pathway activity. We also observed that LINC01133 promoted the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) of pancreatic cancer cells. We subsequently evaluated the effect of LINC01133 on the Wnt/β-catenin pathway and confirmed that LINC01133 can interact with Enhancer Of Zeste Homolog 2 (EZH2) and then promote H3K27 trimethylation. This can further silence AXIN2 and suppress GSK3 activity, ultimately activating β-catenin. Collectively, these data indicate that exosomal LINC01133 plays an important role in pancreatic tumor progression, and targeting LINC01133 may provide a potential treatment strategy for PDAC.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yuyun Wu ◽  
Ningbo Hao ◽  
Suming Wang ◽  
Xin Yang ◽  
Yufeng Xiao ◽  
...  

Gastric cancer (GC) is one of the most common malignancies worldwide, and the tumor metastasis leads to poor outcomes of GC patients. Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules that play a crucial role in tumor metastasis. However, the biological function and underlying mechanism of numerous lncRNAs in GC metastasis remain largely unclear. Here, we report a novel lncRNA, lnc-TLN2-4:1, whose expression is decreased in GC tissue versus matched normal tissue, and its low expression is involved in the lymph node and distant metastases of GC, as well as poor overall survival rates of GC patients. We further found that lnc-TLN2-4:1 inhibits the ability of GC cells to migrate and invade but does not influence GC cell proliferation and confirmed that lnc-TLN2-4:1 is mainly located in the cytoplasm of GC cells. We then found that lnc-TLN2-4:1 increases the mRNA and protein expression of TLN2 in GC cells and there is a positive correlation between the expression of lnc-TLN2-4:1 and TLN2 mRNA in GC tissue. Collectively, we identified a novel lncRNA, lnc-TLN2-4:1, in GC, where lnc-TLN2-4:1 represses cell migration and invasion. The low expression of lnc-TLN2-4:1 is associated with poor overall survival rates of GC patients. These suggest that lnc-TLN2-4:1 may be a tumor suppressor during GC metastasis.


2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Dongyun Lei ◽  
Lechun Lv ◽  
Li Yang ◽  
Wenjuan Wu ◽  
Yong Liu ◽  
...  

Chronic actinic dermatitis (CAD), a photosensitive dermatosis, is characterized by inflammatory lesions, especially on sun-exposed skin. However, its pathogenesis remains unclear. In this study, second-generation RNA sequencing and comprehensive bioinformatics analyses of mRNAs and long noncoding RNAs (lncRNAs) were performed to determine the transcriptome profiles of patients with CAD. A total 6889 annotated lncRNAs, 341 novel lncRNAs, and 65091 mRNAs were identified. Interestingly, patients with CAD and healthy controls showed distinct transcriptome profiles. Indeed, 198 annotated (81.48%) and 45 novel (18.52%) lncRNAs were differentially expressed between the two groups. GO, KEGG, and RGSEA analyses of lncRNAs showed that inflammatory and immune response related pathways played crucial roles in the pathogenetic mechanism of CAD. In addition, we unveiled key differentially expressed lncRNAs, including lncRNA RP11-356I2.4 which plays a role probably by regulating TNFAIP3 and inflammation. qRT-PCR data validated the differentially expressed genes. The newly identified lncRNAs may have potential roles in the development of CAD; these findings lay a solid foundation for subsequent functional exploration of lncRNAs and mRNAs as therapeutic targets for CAD.


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