Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing

Voellenkle, Christine; García-Manteiga, José Manuel; Pedrotti, Simona; Perfetti, Alessandra; Toma, Ilario De; Silva, D. Da; Maimone, Biagina; Greco, Simona; Fasanaro, Pasquale; Creo, Pasquale; Zaccagnini, Germana; Gaetano, Carlo; Martelli, Fabio

doi:10.1038/srep24141

Cited by 127 publications

(120 citation statements)

References 59 publications

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“…We speculated that the lncRNAs stimulated by oxidative stress may trigger inflammation in CCA. To identify whether any lncRNA related with inflammation is regulated by oxidative stress, we firstly reanalyzed several GEO data, GSE76743 [29], GSE57539 [30], GSE67106 [31], GSE55146 [32], and GSE70544 [33], and identified 40 lncRNAs responding to oxidative stress or inflammatory response (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

et al. 2016

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BackgroundLong non-coding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression.MethodsIn this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP) was performed to explore the mechanism of miRNA-lncRNA sponging.ResultsWe firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs) by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4.ConclusionsOur study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and may serve as novel targets for the development of new countermeasures of CCA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0348-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

et al. 2016

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“…In order to further explore the relationship between the cellular genes affected by KSHV infection and those affected by hypoxia, we analyzed the reported results of two studies of human umbilical vein endothelial cells (HUVECs) [51,52]. KS spindle cells are thought to be derived from endothelial cells, and HUVECs can thus potentially provide more insight into the pathogenesis of KS than SLK cells.…”

Section: Resultsmentioning

confidence: 99%

“…KS spindle cells are thought to be derived from endothelial cells, and HUVECs can thus potentially provide more insight into the pathogenesis of KS than SLK cells. One study used microarray to analyze the genes whose expression was modulated by de novo KSHV infection of HUVECs (48 hrs post-infection) [51], while the other used RNA sequencing to analyze HUVECs exposed to hypoxia (1% O 2 ) for 48 hrs [52]. Overall, there were 8,863 genes that were analyzed in both studies, of which 350 were dysregulated by de novo KSHV infection and 1,137 were dysregulated by hypoxia (using a 1.5 fold cut-off for both parameters).…”

Section: Resultsmentioning

confidence: 99%

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

et al. 2017

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Kaposi sarcoma-associated herpesvirus (KSHV) causes several tumors and hyperproliferative disorders. Hypoxia and hypoxia-inducible factors (HIFs) activate latent and lytic KSHV genes, and several KSHV proteins increase the cellular levels of HIF. Here, we used RNA sequencing, qRT-PCR, Taqman assays, and pathway analysis to explore the miRNA and mRNA response of uninfected and KSHV-infected cells to hypoxia, to compare this with the genetic changes seen in chronic latent KSHV infection, and to explore the degree to which hypoxia and KSHV infection interact in modulating mRNA and miRNA expression. We found that the gene expression signatures for KSHV infection and hypoxia have a 34% overlap. Moreover, there were considerable similarities between the genes up-regulated by hypoxia in uninfected (SLK) and in KSHV-infected (SLKK) cells. hsa-miR-210, a HIF-target known to have pro-angiogenic and anti-apoptotic properties, was significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Interestingly, expression of KSHV-encoded miRNAs was not affected by hypoxia. These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and that a substantial portion of hypoxia-induced changes in cellular gene expression are induced by KSHV infection. Therefore, targeting hypoxic pathways may be a useful way to develop therapeutic strategies for KSHV-related diseases.

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“…Also, recent evidence has proved that lncRNA are also important for the biological function of endothelial cells and lncRNA expression profile is altered in response to stimulus or hyperglycemia in endothelial cells [10][11][12][13][14]. But nothing is known about the lncRNA profile alteration of lymphatic endothelial cells in type 2 diabetes [15,16].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Long Non-Coding RNA Expression of Lymphatic Endothelial Cells in Response to Type 2 Diabetes

Qi¹,

Zhou²,

Zeng³

et al. 2017

Cell Physiol Biochem

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Background: Recent evidence has indicated that long non-coding RNA (lncRNA) is involved in the pathogenesis of type 2 diabetes, but nothing is known about lncRNA expression changes of lymphatic endothelial cells in response to type 2 diabetes. Methods: The GSE38396 dataset was downloaded from the Gene Expression Omnibus database and the probe sets of Human Gnome U133 Plus2.0 microarray were annotated for lncRNA. Differentially expressed lncRNAs between diabetic and non-diabetic lymphatic endothelial cells were calculated. Results: Compared with lymphatic endothelial cells in non-diabetic patients, 31 lncRNAs were down-regulated and 79 lncRNAs were up-regualted in lymphatic endothelial cells of type 2 diabetic patients. Several known lncRNAs were found, such as H19, GAS5, UCA1, CRNDE, GAS5, and LINC00312. Co-expression network of differentially expressed lncRNAs and mRNAs were constructed. Based on genomic regions of these lncRNAs, we found that binding sites of MAF and TCF3 were enriched and these lncRNAs may be related to insulin reporter signaling pathway and response to insulin stimulus. Conclusions: In a word, we found a set of lncRNAs were differentially expressed in lymphatic endothelial cells in response to type 2 diabetes and these lncRNAs may be involved in the pathogenesis of diabetes-related complications.

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Implication of Long noncoding RNAs in the endothelial cell response to hypoxia revealed by RNA-sequencing

Cited by 127 publications

References 59 publications

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

RNA Sequencing Reveals that Kaposi Sarcoma-Associated Herpesvirus Infection Mimics Hypoxia Gene Expression Signature

Analysis of Long Non-Coding RNA Expression of Lymphatic Endothelial Cells in Response to Type 2 Diabetes

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