Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Enhanced Myd88 expression has been found in various parenchymal tumors especially in hepatocellular carcinoma with little mechanism of its upregulation known. A lot of long non-coding RNAs are reported to regulate the protein-coding genes which have location association through various mechanisms. In our study we confirmed a new long non-coding RNA Myd88 aberrant upregulated in HCC located upstream of Myd88 and verified a positive regulation relationship between them indicating that Lnc-Myd88 might participate in the enhanced expression of Myd88 in HCC. The gain- and loss-of-function analysis revealed that Lnc-Myd88 could promote the proliferation and metastasis of HCC both in vitro and in vivo. In addition, ChIP assays demonstrated that Lnc-Myd88 might increase Myd88 expression through enhancing H3K27Ac in the promoter of Myd88 gene, thus resulting in the activation of both NF- κB and PI3K/AKT signal pathways. In conclusion, we proposed that Lnc-Myd88 might serve as a novel diagnosis and therapeutic target for HCC.

Related collections

Most cited references 25

Record: found
Abstract: found
Article: not found

Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin.

Jin-feng Huang, Ying-jun Guo, Chen-xi Zhao … (2013)

The hepatitis B virus X protein (HBx) has been implicated as an oncogene in both epigenetic modifications and genetic regulation during hepatocarcinogenesis, but the underlying mechanisms are not entirely clear. Long noncoding RNAs (lncRNAs), which regulate gene expression with little or no protein-coding capacity, are involved in diverse biological processes and in carcinogenesis. We asked whether HBx could promote hepatocellular carcinoma (HCC) by regulating the expression of lncRNAs. In this study we investigated the alteration in expression of lncRNAs induced by HBx using microarrays and real-time quantitative polymerase chain reaction (PCR). Our results indicate that HBx transgenic mice have a specific profile of liver lncRNAs compared with wildtype mice. We identified an lncRNA, down-regulated expression by HBx (termed lncRNA-Dreh), which can inhibit HCC growth and metastasis in vitro and in vivo, act as a tumor suppressor in the development of hepatitis B virus (HBV)-HCC. LncRNA-Dreh could combine with the intermediate filament protein vimentin and repress its expression, and thus further change the normal cytoskeleton structure to inhibit tumor metastasis. We also identified a human ortholog RNA of Dreh (hDREH) and found that its expression level was frequently down-regulated in HBV-related HCC tissues in comparison with the adjacent noncancerous hepatic tissues, and its decrement significantly correlated with poor survival of HCC patients. These findings support a role of lncRNA-Dreh in tumor suppression and survival prediction in HCC patients. This discovery contributes to a better understanding of the importance of the deregulated lncRNAs by HBx in HCC and provides a rationale for the potential development of lncRNA-based targeted approaches for the treatment of HBV-related HCC. Copyright © 2012 American Association for the Study of Liver Diseases.

0 comments Cited 151 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches.

Tim F Greten, Xin Wang, Firouzeh Korangy (2015)

The recent approval of two immune checkpoint inhibitors for the treatment of malignant melanoma has sparked great interest by physicians and basic scientists searching for novel therapeutics for GI cancer. Chronic inflammation is recognised as a major risk factor for the development of hepatocellular carcinoma (HCC) and makes this type of cancer a potentially ideal target for an immune based treatment approach. Further evidence for a critical role of immune responses in patients with HCC is derived from the fact that immune signatures and profiles predict patients' outcome as well as the fact that tumour-induced spontaneous antitumour immunity can be detected. In addition ablative therapies can lead to changes in the number, phenotype and function of different immune cell subsets, which correlate with patients' survival. Various HCC-specific mouse models have been developed, which improve our understanding of hepatocarcinogenesis and tumour-immune cell interactions, and lead to the development of novel immune based treatment approaches, which are currently being evaluated in preclinical and in early clinical settings. Immune checkpoint blockade along with adoptive immune cell therapy and vaccine approaches are currently being evaluated either alone or in combination with other treatments. Here, we provide an overview for the rationale of immunotherapy in HCC, summarise ongoing studies and provide a perspective for immune based approaches in patients with HCC.

0 comments Cited 93 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature

Yolanda Sanchez, Victor Segura-Ibarra, Oskar Marín-Béjar … (2014)

The transcription factor p53 is the most prominent human tumour suppressor. p53 is essential for the cellular response to DNA-damaging stimuli to maintain genomic integrity of cells, mainly by activating a gene expression programme that leads to cell cycle arrest or elimination of the damaged cells through programmed cell death. The vast majority of the p53 downstream effects are mediated through its intrinsic nature as transcription factor1. On cellular stress, p53 protein is stabilized and can recognize its target genes through binding to a consensus response element (p53RE) located proximal to the transcription start site (TSS) at the gene promoter, the first intron or even further downstream of the gene2. For decades, researchers have focused their attention on the protein-coding genes regulated by p53, which led to the discovery of a large set of proteins involved in the p53 response. However, recent progress has suggested that a significant number of p53REs lie on noncoding regions of the genome and that some of these genomic loci are transcribed into long noncoding RNAs (lncRNAs). LncRNAs are transcripts longer than 200 nucleotides that lack functional open reading frames3 4. Similarly to mRNAs, lncRNAs are frequently polyadenylated and spliced, and their promoters are subjected to regulation by transcription factors such as p53. Distinctive features of lncRNAs are their highly specific expression patterns and relatively low conservation across species, consistent with their role as regulatory molecules that fine-tune gene expression4 5 6 7. Few lncRNAs have been studied in some depth. These show the important roles of lncRNAs in many processes that involve gene regulation, such as cellular differentiation, proliferation, dosage compensation and chromosomal imprinting3 8 9 10 11 12. Given their physiological activities, the deregulation of lncRNAs is one of the underlying causes of human disease, including cancer, and they emerge as promising targets for novel therapies13 14 15. Our work and others’ have shown that p53 regulates the expression of some lncRNAs. For instance, we identified lincRNA-p21 (ref. 16) and Pint 17, which modulate cellular apoptosis and proliferation in mouse cells. Studies by other groups lead to the identification of PANDA 18, a lncRNA able to inhibit cellular apoptosis in human fibroblasts, lincRNA-RoR and loc285194 (refs 19, 20), reported as post-tanscriptional regulators in the p53 pathway, and TUG-1, which controls proliferation in human non-small cell lung cancer4 21. Although these studies underscore a functional role of lncRNAs in the p53 pathway, the extent of the contribution of lncRNAs to the p53 response to DNA damage in human cells still remains poorly understood. In this study, we integrate genome-wide expression data obtained by RNA sequencing (RNA-seq) with p53 ChIP-seq data of human cancer cells treated or not with a DNA-damaging drug. The combination of these experimental approaches allowed us to relate the active binding of p53 to the expression of protein-coding and -noncoding regions of the genome, including regions poorly or not annotated previously. We also provide experimental evidence of the contribution of a subset of lncRNAs to the p53 human transcriptional network and biological activity. Finally, we show a tumour suppressor signature defined by p53-regulated lncRNAs. Results Hundreds of lncRNAs are affected by DNA-damage treatment in human cells We set out to investigate the polyadenylated human transcriptome regulated by p53. To that end, we used as a model the HCT116 colorectal cancer cell line, which has been previously reported to have an intact p53 response22 (Supplementary Fig. 1a). To induce p53 protein stabilization and transcription of its target genes, cells were treated with the DNA-damage-inducing drug 5-fluorouracil (5-FU) for different times (0, 4 and 12 h). We then isolated the polyadenylated RNA fraction and performed strand-specific paired-end RNA Illumina sequencing with reads of 150 base pairs (bp) length (Supplementary Fig. 1b). On average, we obtained 170M mapped reads per experimental condition, which were assembled using Cufflinks and Cuffmerge23 (See Methods and Suplementary Methods). In total, 131,936 transcripts were successfully assembled, of which 85% were annotated according to Gencode v19 (refs 24, 25). Out of the annotated transcripts, 76% (85,865) were identified as protein-coding mRNAs, while the remaining 24% were classified as different types of noncoding transcripts. A total of 14% (15,776) were defined as lncRNAs, including antisense, intergenic, processed transcripts, sense-overlapping and sense-intronic lncRNAs, while the remaining 10% (6,825) of annotated transcripts corresponded to other types of noncoding RNAs, such as transcripts derived from pseudogenes, retained introns and pri-microRNAs (Fig. 1a). This relative distribution of transcripts is similar to that described by Encode25. We also found a large number of unassigned transcripts (20,092), many of which were unspliced and which could partially be an artefact caused by incomplete determination of the transcript structures. To address this point, we analysed publicly available ChIP-seq data from HCT116 cells26. While the genomic region ranging from −5kb to +5kb around the 5′ end of 83% of the unassigned transcripts defined by our RNA-seq was not associated with an active transcription chromatin mark (that is, H3K4me3, H3K4me1 or H3K27Ac; Fig. 1c), the remaining 17% were enriched by at least one of these histone marks at their 5′ end, suggesting the presence of a promoter driving their expression. Next, to determine what transcripts are perturbed by the DNA-damage treatment, we applied Cuffdiff 2 (ref. 27; see Methods). Comparing HCT116 cells treated with DNA damage for 12 h to untreated cells, 4,050 transcripts were found differentially expressed (P 0, limma B-statistics or log odds; Supplementary Table 6). Interestingly, the relationship between p53 and these two lncRNAs was confirmed by the prediction of p53 as a significant upstream regulator for both sets of genes (P=2.12E−05 for PR-lncRNA-1 and P=1.00E−12 for PR-lncRNA-10, Ingenuity Fisher’s exact test). The gene expression changes observed by microarray analysis were validated in independent experiments where we transfected separately the individual ASOs to knockdown the lncRNAs and performed qRT–PCR for a panel of representative genes. We confirmed the expression changes for 12 out of 17 (PR-lncRNA-1) and 16 out of 18 (PR-lncRNA-10) differentially expressed genes. Few mRNAs that did not show a statistically significant differential expression by qRT–PCR, still showed the same trend (up- or downregulated) observed in the microarray analysis (Supplementary Figs 4a and 5a). In addition, we performed independent validations by transfecting the ASOs into HCT116 p53−/− cells with or without DNA-damage treatment. Under these conditions, we could not detect any effect of the ASO treatment on the validation gene set, confirming that the effects observed are specific of the p53-dependent expression of PR-lncRNA-1 and PR-lncRNA-10 (Supplementary Figs 4b,c and 5b,c). We next compared the effect of PR-lncRNA-1 and PR-lncRNA-10 depletion with the observed gene expression changes caused by DNA damage in HCT116 cells. Out of the 69 protein-coding genes regulated by PR-lncRNA-1 that consistently changed with DNA-damage treatment, many were related to induction of apoptosis and proliferation. For instance, we found the apoptosis regulators BCL2L and BIRC3, the DNA polymerase subunit POLA1 or the growth factor TGFB2 (Fig. 4c,d; Supplementary Table 7). On the other hand, 109 of the protein-coding genes regulated by PR-lncRNA-10 constituted another component of the DNA-damage response, and included the cell cycle inhibitor CDKN1A, the transcription factor JUNB or the apoptosis regulators BIRC6, TP53I3 and FAS among many others (Fig. 4c,d; Supplementary Table 7). In agreement with a potential role of these lncRNAs in the p53 response to DNA damage, p53 was found to be the most significant predicted upstream regulator and enriched pathway for the sets of genes affected by both DNA damage and PR-lncRNA-1 or PR-lncRNA-10 (P=1.0E−07 or P=2.1E−03, respectively). This is illustrated by the network depicted in Fig. 4d, which represents the predicted relationships between some of the genes co-regulated by p53 and PR-lncRNA-1 or PR-lncRNA-10. Altogether, the results shown here suggest that PR-lncRNA-1 and PR-lncRNA-10 are active components of the p53 transcriptional response and that they modulate the gene expression response to DNA damage downstream of p53. PR-lncRNAs required for efficient binding of p53 to gene targets Our results showed that PR-lncRNA-1 and PR-lncRNA-10 are not just directly regulated by p53, but are involved in the regulation of genes of the p53 pathway. We then investigated how these lncRNAs could affect the expression of their targets. While the microarray analysis showed changes in the steady-state levels of the mRNAs regulated by PR-lncRNA-1 and PR-lncRNA-10, it did not distinguish whether the changes are taking place at the transcriptional or post-transcriptional level. To address this point, we analysed the stability of PR-lncRNA-1 and PR-lncRNA-10 target mRNAs upon knockdown of the lncRNAs by blocking their transcription with actinomycin-D treatment. These experiments did not show significant changes in the stability of the mRNAs analysed, suggesting that PR-lncRNA-1 and PR-lncRNA-10 do not act post-transcriptionally on these mRNAs, but rather regulate their expression at the transcriptional level (Supplementary Fig. 6). As discussed above, the transcription factor p53 is predicted to be the upstream regulator of the genes affected by PR-lncRNA-1 and PR-lncRNA-10 knockdowns. We therefore hypothesized that PR-lncRNA-1 and PR-lncRNA-10 could affect p53 activity. We excluded the possibility that p53 gene expression was affected, as the microarray analyses and additional qRT–PCR validations clearly showed that p53 mRNA levels were not changed on PR-lncRNA-1 nor PR-lncRNA-10 knockdown (Supplementary Figs 4 and 5). As p53 is tightly regulated at the protein level, we analysed total p53 protein level in PR-lncRNA-1 and PR-lncRNA-10 knockdown conditions. However, we did not detect any differences upon knockdown of the lncRNAs (Fig. 5a,b). Similarly, we did not detect any changes in the levels of phosphorylated p53 protein at serine 15, which is generally thought to be involved in the activation of p53 after DNA damage30. We concluded that neither PR-lncRNA-1 nor PR-lncRNA-10 affects p53 protein levels or phosphorylation. We then tested whether the ability of p53 to transcriptionally activate some target genes could be influenced by PR-lncRNA-1 or PR-lncRNA-10. To that end, we selected a set of genes that are p53 direct transcriptional targets, that is, are directly bound by p53 and change their expression on DNA damage (SERPINB5, FAS, CDKN1A, BCL2L1, BBC3, BAX and MDM2; see Supplementary Table 3). Most of the selected genes (SERPINB5, FAS, CDKN1A and BCL2L1) were also found altered in our microarray analysis by the knockdown of PR-lncRNA-1 and/or PR-lncRNA-10 (Supplementary Table 8; Fig. 4c,d). We then performed p53 ChIP in the presence and absence of PR-lncRNA-1 or PR-lncRNA-10 depletion. On PR-lncRNA-1 and/or PR-lncRNA-10 depletion, we observed a significant decrease in the binding of p53 to the p53REs of SERPINB5, CDKN1A, BCL2L1 and BBC3 genes, although the decrease was generally more pronounced on PR-lncRNA-10 inhibition (Fig. 5c). Furthermore, when the mRNA levels were quantified in the same experiments, we observed a decrease in the expression of the genes in correlation with the decrease in p53 binding to their promoters upon the lncRNAs depletion (Fig. 5d). Taken together, these results suggest that p53 requires PR-lncRNA-10 and, in lesser extent, PR-lncRNA-1 to efficiently bind and activate some of its direct transcriptional targets. PR-lncRNA-1 and PR-lncRNA-10 are negative regulators of cell survival and proliferation The gene expression analysis revealed that PR-lncRNA-1 and PR-lncRNA-10 modulate the expression of several genes related to cell cycle control and apoptosis induction, which are the major functional outcomes of p53 activation. To determine the role of the p53-regulated lncRNAs in this context, we monitored cell proliferation after depletion of PR-lncRNA-1 or PR-lncRNA-10 in the presence or absence of DNA-damage induction. HCT116 cells were treated with doxorubicin (doxo) to induce DNA damage, as this drug induces expression of p53 and its target genes, including PR-lncRNA-1 and PR-lncRNA-10 (Supplementary Fig. 7a,b), but is not as strong apoptosis inducer as 5-FU, allowing us to carry out experiments for several days. Cell proliferation assays were performed with HCT116 cells showing a significant increase in the number of viable cells when depleted of PR-lncRNA-1 or PR-lncRNA-10 compared with the controls (Supplementary Fig. 7c,d), both in the presence and absence of drug treatment, although the difference in proliferation between lncRNA-depleted cells and controls was more marked in cells treated with DNA damage (Fig. 6a,b). These results suggested that both PR-lncRNA-1 and PR-lncRNA-10 may contribute to the p53 pro-apoptotic and/or cell cycle regulatory functions. The major effect of DNA damage on HCT116 cells is a generalized cellular apoptosis, which reaches ~40% within 12 h of 5-FU treatment (Fig. 6, Supplementary Fig. 5e). To evaluate the role of the lncRNAs under investigation in this cellular mechanism, we quantified the number of apoptotic cells following depletion of PR-lncRNA-1 or PR-lncRNA-10 under DNA-damage conditions. Consistent with the effect observed in proliferation, we found a significant decrease in the number of apoptotic cells measured by annexin V detection, reaching close to 50% reduction under the best knockdown conditions (Figs 6c and 4a; Supplementary Fig. 7f,g). This effect was more pronounced when PR-lncRNA-1 was inhibited compared with PR-lncRNA-10 inhibition (55 and 43% of reduction, respectively), and was confirmed by quantifying caspase3/7 levels under similar experimental conditions (Fig. 6d,e). We therefore concluded that PR-lncRNA-1 and PR-lncRNA-10 contribute to apoptosis induction by DNA damage. p53 activity as a tumour suppressor involves also a tight control of cell cycle progression, p53 being able to control both G1 and G2/M checkpoints31. To further characterize the biological role of the two p53-regulated lncRNAs, we carried out cell cycle analysis of HCT116 cells depleted of the lncRNAs both in the presence or absence of DNA damage (doxo or 5-FU). When either PR-lncRNA-1 or PR-lncRNA-10 was depleted, and in all the experimental conditions tested, we observed a significant increase of cells in S-phase of cell cycle consistent with the increase in cell proliferation observed under the same conditions (Fig. 6f–i; Supplementary Fig. 7h,i). As for the cell proliferation assays, the differences observed in the cell cycle phase distribution between lncRNAs-depleted cells and controls were more pronounced following DNA damage compared with untreated cells (Fig. 6f–i; Supplementary Fig. 7h,i). These results suggest that both PR-lncRNA-1 and PR-lncRNA-10 contribute to cell cycle regulation, playing a role even when expressed at basal levels, as observed with cells not treated with DNA-damage drugs. However, their roles in cell cycle progression appeared more pronounced under DNA-damage conditions, suggesting a major role for the lncRNAs in the DNA-damage response. Altogether, we show that the p53-regulated PR-lncRNA-1 and PR-lncRNA-10 contribute to the biological outcome of the p53 pathway activation by promoting apoptosis and cell cycle arrest. PR-lncRNAs constitute a tumour suppressor signature p53 malfunction is well known to play a major role in the development of cancer. A total of 60% of non-hypermutated tumours harbour mutations in the p53 gene32 33, and 70% of colorectal carcinomas show loss of heterozygosity in 17p, where p53 gene locus resides34 35. The results obtained for PR-lncRNA-1 and PR-lncRNA-10 suggest their involvement in the p53 tumour suppression function in colorectal cancer cells. We therefore hypothesized that their expression levels, as well as the expression of other p53-regulated lncRNAs, could be altered in human primary colorectal cancer specimens. To corroborate this hypothesis, we analysed the expression of the p53 directly regulated lncRNAs identified in this study in a cohort of human colon adenocarcinoma healthy tissue-paired samples. In agreement with a potential role of the lncRNAs in tumour suppression, the expression levels of all the lncRNAs analysed were lower in colorectal tumours compared with normal tissue, although changes only reached significance (P 0. Functional enrichment analysis of Gene Ontology (GO) categories was carried out using standard hypergeometric test43. The biological knowledge extraction was complemented through the use of Ingenuity Pathway Analysis (Ingenuity Systems; www.ingenuity.com). qPCR primers and ASOs The qPCR primers and ASO sequences used in this study are listed in Supplementary Table 9. All ASOs were designed and provided by ISIS Pharmaceuticals. All were 20 nt in length and chemically modified with phosphorothioate in the backbone, five 2′-O-methoxyethyl residues at each terminus and a central deoxynucleotide region of 10 residues (5-10-5 gapmer). ASOs were synthesized using an Applied Biosystems 380B automated DNA synthesizer (PerkinElmer Life and Analytical Sciences-Applied Biosystems). Cell proliferation assays For proliferation analysis, 1,000 cells were plated per well in 96-well plates and assessed with a CellTiter96 Aqueous Non-Radioactive Cell Proliferation Assay (MTS) Kit G3581 (Promega). Apoptosis and cell cycle analysis At 24 h after transfection, 1 × 105 cells were plated in 96-well white microplates and treated for 24 h with 385 μM 5-FU. Apoptosis was determined by quantification with caspase-Glo 3/7 reagent (Promega) using a FLUOstar Optima luminometer, and with annexin V fluorescence-activated cell sorting using an Apoptosis Detection Kit I (cat-559763; BD Biosciences). For cell cycle analysis, cells were labelled with propidium iodide (PI) and measured in the FACSCalibur flow cytometer (BD Biosciences). Data represent the mean±s.d. of a minimum of three biological replicates. Human samples Human colorectal carcinoma samples were provided by the Basque Biobank for Research-OEHUN (http://www.biobancovasco.org). Samples were processed following standard operation procedures with appropriate ethical approval by the Ethics Committee for Clinical Research of Donostia Hospital. An informed consent was obtained from all subjects. RNA was extracted with RNEASY MINI KIT (Qiagen) and reverse transcription was performed using random priming and Superscript Reverse Transcriptase (Life Technologies), according to the manufacturer’s guidelines. The ▵C t value was determined by subtracting the GAPDH C t value from the p53-regulated lncRNAs’ C t value. The performance as biomarker of each lncRNA was evaluated using ROC analysis44. An algorithm based on logistic regression was applied to the obtained 5-lncRNA-signature classification45. Subcellular fractionation A total of 107 cells were trypsinized and washed once with cold PBS, aliquoted in two tubes and collected by centrifugation at 1,000g for 5 min at 4 °C. One cell pellet represented the whole-cell extract, while the other one was processed for the remaining subcellular fractions. Both pellets were resuspended in 500 μl of Buffer A (10 mM Tris-HCl, pH 7.5, 1.5 mM MgCl2, 140 mM NaCl, 0.05 IGEPAL supplemented with protease inhibitor cocktail and SuperaseIN 10 U ml−1), incubated for 10 min on ice and kept for subsequent RNA extraction. A total of 500 μl of Buffer A plus sucrose (10 mM Tris-HCl, pH 7.5, 1.5 mM MgCl2, 140 mM NaCl 0.05% IGEPAL, 50% Sucrose) was added to the bottom of a clean eppendorf tube and the upper phase (whole-cell extract resuspended in Buffer A) was gently added to this tube preventing the mix of the two phases and centrifuged for 10 min at 4 °C and 12,000g to obtain nuclear and cytoplasmic fractions. Around 500 μl of the upper phase (cytoplasmic fraction) was collected and the rest was discarded, leaving the pellet (nuclear fraction). Total nuclear fraction was resuspended in 500 μl of Buffer B (10 mM Tris, 100 mM NaCl, 1 mM EGTA, 300 mM sucrose, 0.5 mM NaVO3, 50 mM NaF, 1 mM phenylmethylsulphonyl fluoride, 0.5% triton X-100, protease inhibitor cocktail and SuperasIN) and incubated for 10 min on ice to permeabilize the cells. To separate nuclear soluble from nuclear insoluble fraction, sample was centrifuged at 2,000 g for 5 min at 4 °C and the supernantant (nuclear soluble fraction) and pellet (nuclear insoluble/chromatin fraction) were collected. The nuclear insoluble fraction was resuspended in Buffer A and finally 1 ml of Trizol was added to all tubes for subsequent RNA extraction. RNA fluorescence in situ hybridization RNA fluorescence in situ hybridization for PR-lncRNA-1 and PR-lncRNA-10 detection was performed using a pool of 48 fluorescent probes purchased from Stellaris Biosearch Technologies, following the manufacturer’s instructions. Statistical analysis Experimental data are represented as the mean±s.d. of a minimum of three biological replicates and were compared using Student’s t-test. Significant P values are indicated with asterisks as follows: *P 0). Supplementary Data 8 Genes differentially expressed upon DNA damage (RNA-seq analysis) and affected by PR-lncRNA-1 or PR-lncRNA-10 inhibition. Supplementary Data 9 Sequences of oligonucleotides used in this study .

0 comments Cited 90 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cell Death Dis

Journal ID (iso-abbrev): Cell Death Dis

Title: Cell Death & Disease

Publisher: Nature Publishing Group

ISSN (Electronic): 2041-4889

Publication date (Print): October 2017

Publication date (Electronic): 12 October 2017

Publication date PMC-release: 1 October 2017

Volume: 8

Issue: 10

Page: e3124

Affiliations

[1 ]Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University , Nanjing, Jiangsu Province, PR China

[2 ]Department of General Surgery, Huai'an First People's Hospital, Nanjing Medical University , Huai'an, Jiangsu Province, PR China

[3 ]The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University , Changzhou, Jiangsu Province, PR China

Author notes

[* ]Transplantation Center, The First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province 210029, China . Tel: +86 25 68136746; Fax: +86 25 86560946; E-mail: sunbc@ 123456njmu.edu.cn

[* ]The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, Changzhou, Jiangsu Province, China . Tel: +86 519 81087258; Fax: +86 519 88166558; E-mail: qinxihu@ 123456126.com

[4]

These authors contributed equally to this work.

Article

Publisher Item ID: cddis2017519

DOI: 10.1038/cddis.2017.519

PMC ID: 5682683

PubMed ID: 29022910

SO-VID: a0a5e2a2-dfd1-44c7-a231-b2d3d25613bf

License:

Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

History

Date received : 22 March 2017

Date revision received : 11 August 2017

Date accepted : 22 August 2017

Comments

Comment on this article

scite_

Cited by 17

See all cited by

Most referenced authors 329

See all reference authors

- Version 1

Long non-coding RNA Myd88 promotes growth and metastasis in hepatocellular carcinoma via regulating Myd88 expression through H3K27 modification

Read this article at

Abstract

Related collections

Claudins

Most cited references 25

Hepatitis B virus X protein (HBx)-related long noncoding RNA (lncRNA) down-regulated expression by HBx (Dreh) inhibits hepatocellular carcinoma metastasis by targeting the intermediate filament protein vimentin.

Current concepts of immune based treatments for patients with HCC: from basic science to novel treatment approaches.

Genome-wide analysis of the human p53 transcriptional network unveils a lncRNA tumour suppressor signature

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 259

Cited by 17

Most referenced authors 329