Identification of potential long noncoding RNA associated with nasopharyngeal carcinoma using deep sequencing.
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ABSTRACT:
SUBMITTER: Xu YZ
PROVIDER: S-EPMC6683893 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
Publications
Identification of potential long noncoding RNA associated with nasopharyngeal carcinoma using deep sequencing.
Xu Yu-Zhong YZ Chen Fang-Fang FF Zhang Yu Y Liang Hui H Li Xiao-Jun XJ He Chen C
The Journal of international medical research 20190524 7
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Project description:BackgroundRecent studies suggested that non-protein-coding genes are implicated in the tumorigenic process of nasopharyngeal carcinoma (NPC). In the present study, we aimed to identify the differentially expressed long noncoding RNA (lncRNA) using data available in the public domain.MethodsMicroarray data set GSE12452 was reannotated with ncFANs. Real-time quantitative PCR was used to quantify and validate the identified lncRNAs in NPC.ResultsIn primary NPC, upregulation of lnc-C22orf32-1, lnc-AL355149.1-1, and lnc-ZNF674-1 was observed. High levels of lnc-C22orf32-1 and lnc-AL355149.1-1 were significantly associated with the male patients. In addition, increased expression of lnc-C22orf32-1 and lnc-ZNF674-1 was associated with advanced tumor stages. Recurrent NPC displayed a distinctive lncRNA expression pattern. lnc-BCL2L11-3 was significantly increased in the recurrent NPC tissues. In addition, significant reduction of lnc-AL355149.1-1 and lnc-ZNF674-1 was observed in the recurrent NPC tissues.ConclusionsOur results demonstrated that it is feasible to identify the differentially expressed lncRNA in the microarray dataset by functional reannotation. The association of lncRNA with gender and tumor size implicated that lncRNA possibly plays a part in the pathogenesis of primary NPC. Further, the distinctive lncRNA identified in the recurrent NPC may reveal a distinctive development mechanism underlying tumor recurrence.
| S-EPMC4009106 | biostudies-literature
Project description:BackgroundThe long noncoding RNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is a critical player in various cancers. However, the clinical value and functional mechanisms of AFAP1-AS1 during the tumorigenicity of nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the clinical application and potential molecular mechanisms of AFAP1-AS1 in NPC tumorigenesis and progression.MethodsThe expression level of AFAP1-AS1 was determined by qRT-PCR in 10 paired fresh human NPC tissues and adjacent normal tissues. RNAscope was performed on 100 paired paraffin-embedded NPC and adjacent nontumor specimens. The biological functions of AFAP1-AS1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays were performed to detect and identify the AFAP1-AS1-interacting protein KAT2B. Protein-RNA immunoprecipitation (RIP) assays were conducted to examine the interaction of AFAP1-AS1 and KAT2B. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of transcription intermediary factor 1 alpha (TIF1α) and H3K14ac on the RBM3 promoter.ResultsAFAP1-AS1 is upregulated in NPC and is a poor prognostic indicator for survival in NPC patients. AFAP1-AS1 was required for NPC proliferation in vitro and tumorigenicity in vivo. Mechanistic investigations suggested that AFAP1-AS1 binds to KAT2B and promotes acetyltransferase activation at two residues (E570/D610). KAT2B further promotes H3K14 acetylation and protein binding to the bromo domain of TIF1α. Consequently, TIF1α acts as a nuclear transcriptional coactivator of RBM3 transcription, leading to YAP mRNA stabilization and enhanced NPC tumorigenicity.ConclusionsOur findings suggest that AFAP1-AS1 functions as an oncogenic biomarker and promotes NPC tumorigenicity through enhanced KAT2B acetyltransferase activation and YAP mRNA stabilization.
| S-EPMC7719841 | biostudies-literature
Project description: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.
| S-EPMC4584063 | biostudies-literature
Project description:BackgroundEarly diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC.MethodsExosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples.ResultsWestern blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes.ConclusionsWe identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.
| S-EPMC8011216 | biostudies-literature
Project description:BackgroundMetabolic reprogramming is a hallmark of cancer. However, the roles of long noncoding RNAs (lncRNAs) in cancer metabolism, especially glucose metabolism remain largely unknown.ResultsIn this study, we identified and functionally characterized a novel metabolism-related lncRNA, LINC00930, which was upregulated and associated with tumorigenesis, lymphatic invasion, metastasis, and poor prognosis in nasopharyngeal carcinoma (NPC). Functionally, LINC00930 was required for increased glycolysis activity and cell proliferation in multiple NPC models in vitro and in vivo. Mechanistically, LINC00930 served as a scaffold to recruit the RBBP5 and GCN5 complex to the PFKFB3 promoter and increased H3K4 trimethylation and H3K9 acetylation levels in the PFKFB3 promoter region, which epigenetically transactivating PFKFB3, and thus promoting glycolytic flux and cell cycle progression. Clinically, targeting LINC00930 and PFKFB3 in combination with radiotherapy induced tumor regression.ConclusionsCollectively, LINC00930 is mechanistically, functionally and clinically oncogenic in NPC. Targeting LINC00930 and its pathway may be meaningful for treating patients with NPC.
| S-EPMC8867671 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC), as a unique head and neck cancer type, is particularly prevalent in certain geographic areas such as eastern Asia. Until now, the therapeutic options have been restricted mainly to radiotherapy or chemotherapy. However, the clinical treatment effect remains unsatisfactory even if the combined radio-chemotherapies. Therefore, it is urgently needed to develop effective novel therapies against NPC. In this study, we discovered that lncRNA Hotair was extremely abundant in NPC cells and clinical NPC samples. Further studies showed that Hotair knockdown significantly attenuated both in vitro and in vivo tumor cell growth and angiogenesis. Our study also demonstrated that Hotair promoted angiogenesis through directly activating the transcription of angiogenic factor VEGFA as well as through GRP78-mediated upregulation of VEGFA and Ang2 expression. Therefore, Hotair may serve as a promising diagnostic marker and therapeutic target for NPC patients.
| S-EPMC4826237 | biostudies-literature
Project description:ObjectiveLong noncoding RNAs (lncRNAs) are an important class of genes involved in various biological functions; however, knowledge about lncRNAs in osteoarthritis (OA) is limited. Therefore, the present study aimed to identify which lncRNAs are expressed in OA versus normal cartilage.MethodsTo identify lncRNAs specifically expressed in OA cartilage, expression of lncRNAs in OA cartilage was compared with that in normal cartilage using microarray analysis. The identified differences in expression of lncRNAs were validated by real time polymerase chain reaction (RT-PCR). Furthermore, expression of several key mRNAs associated with OA, including those for matrix metalloproteinase (MMP)-9, MMP-13, bone morphogenetic protein (BMP)-2, COL2A1 and ADAMTS5, was investigated by RT-PCR in OA and normal cartilage.ResultsMicroarray analysis identified 121 lncRNAs that were up- or down-regulated in OA compared with normal tissue, 73 being upregulated and 48 downregulated compared with normal cartilage. Twenty-one of the above differently expressed lncRNAs were up-regulated twofold. Expression of six lncRNAs, including HOTAIR, GAS5, PMS2L2, RP11-445H22.4, H19 and CTD-2574D22.4, was up-regulated in OA compared with normal tissue as validated by RT-PCR after microarray analysis. Expression of mRNA for MMP-9, MMP-13, BMP-2, and ADAMTS5 in OA was significantly greater than in normal cartilage. However, expression of mRNA for COL2A1 was lower in OA than in normal cartilage.ConclusionThe differently expressed lncRNAs may be associated with the pathogenesis of OA. Further functional studies are critical to confirming the function of lncRNAs in OA and to exploring new potential targets for therapy.
| S-EPMC6583210 | biostudies-literature
Project description:Rosacea is a chronic and relapsing inflammatory cutaneous disorder with highly variable prevalence worldwide that adversely affects the health of patients and their quality of life. However, the molecular characterization of each rosacea subtype is still unclear. Furthermore, little is known about the role of long noncoding RNAs (lncRNAs) in the pathogenesis or regulatory processes of this disorder. In the current study, we established lncRNA-mRNA coexpression networks for three rosacea subtypes (erythematotelangiectatic, papulopustular, and phymatous) and performed their functional enrichment analyses using Gene Onotology, KEGG, GSEA, and WGCNA. Compared to the control group, 13 differentially expressed lncRNAs and 525 differentially expressed mRNAs were identified in the three rosacea subtypes. The differentially expressed genes identified were enriched in four signaling pathways and the GO terms found were associated with leukocyte migration. In addition, we found nine differentially expressed lncRNAs in all three rosacea subtype-related networks, including NEAT1 and HOTAIR, which may play important roles in the pathology of rosacea. Our study provided novel insights into lncRNA-mRNA coexpression networks to discover the molecular mechanisms involved in rosacea development that can be used as future targets of rosacea diagnosis, prevention, and treatment.
| S-EPMC7060422 | biostudies-literature
Project description:Identification of cancer-specific target molecules and biomarkers may be useful in the development of novel treatment and immunotherapeutic strategies. We have recently demonstrated that the expression of long noncoding (lnc) RNAs can be cancer-type specific due to abnormal chromatin remodeling and alternative splicing. Furthermore, we identified and determined that the functional small protein C20orf204-189AA encoded by long intergenic noncoding RNA Linc00176 that is expressed predominantly in hepatocellular carcinoma (HCC), enhances transcription of ribosomal RNAs and supports growth of HCC. In this study we combined RNA-sequencing and polysome profiling to identify novel micropeptides that originate from HCC-specific lncRNAs. We identified nine lncRNAs that are expressed exclusively in HCC cells but not in the liver or other normal tissues. Here, DNase-sequencing data revealed that the altered chromatin structure plays a key role in the HCC-specific expression of lncRNAs. Three out of nine HCC-specific lncRNAs contain at least one open reading frame (ORF) longer than 50 amino acid (aa) and enriched in the polysome fraction, suggesting that they are translated. We generated a peptide specific antibody to characterize one candidate, NONHSAT013026.2/Linc013026. We show that Linc013026 encodes a 68 amino acid micropeptide that is mainly localized at the perinuclear region. Linc013026-68AA is expressed in a subset of HCC cells and plays a role in cell proliferation, suggesting that Linc013026-68AA may be used as a HCC-specific target molecule. Our finding also sheds light on the role of the previously ignored 'dark proteome', that originates from noncoding regions in the maintenance of cancer.
| S-EPMC8744898 | biostudies-literature
Project description:Accumulating evidences highlight the critical roles of long noncoding RNAs (lncRNAs) in a variety of cancers. LncRNA PXN-AS1-L was previously shown to exert oncogenic roles in hepatocellular carcinoma. However, the expression, role, and molecular mechanism of PXN-AS1-L in nasopharyngeal carcinoma (NPC) malignancy remain unknown. Here, we determined that PXN-AS1-L is upregulated in NPC tissues and cell lines. Increased expression of PXN-AS1-L predicts worse prognosis of NPC patients. PXN-AS1-L overexpression promotes NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. PXN-AS1-L silencing suppresses NPC cell proliferation, migration, and invasion in vitro. Mechanistically, PXN-AS1-L directly interacts with SAPCD2 mRNA 3'-untranslated region, prevents the binding of microRNAs-AGO silencing complex to SAPCD2 mRNA, and upregulates the mRNA and protein level of SAPCD2. SAPCD2 is also increased in NPC tissues. The expression of SAPCD2 is significantly positively associated with that of PXN-AS1-L in NPC tissues. Gain-of-function and loss-of-function experiments demonstrated that SAPCD2 also promotes NPC cell proliferation, migration, and invasion. Furthermore, depletion of SAPCD2 significantly reverses the roles of PXN-AS1-L in promoting NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. In conclusion, lncRNA PXN-AS1-L is upregulated in NPC and promoted NPC malignancy by upregulating SAPCD2 via direct RNA-RNA interaction.
| S-EPMC6675719 | biostudies-literature