Long non-coding RNA HOXA transcript at the distal tip as a biomarker for gastric cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Yang Y
PROVIDER: S-EPMC5494658 | biostudies-other | 2017 Jul
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Gastric cancer (GC) is a considerable global health burden. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and play important roles in GC. However, only a few lncRNAs have been functionally characterized. In this study, we identified that long intergenic non-protein coding RNA 941 (LINC00941) is a potential biomarker for diagnosis and prognosis from the cancer genome atlas (TCGA), and we found that the expression of LINC00941 is associated with tumor depth and distant metastasis in GC. Furthermore, functional enrichment analysis of LINC00941 co-expression network demonstrated that LINC00941 might be an essential regulator of tumor metastasis and cancer cell proliferation. To validate our findings, we utilized the loss-of-function analysis to reveal the biological function of LINC00941 in GC cells. Loss-of-function analysis revealed that silence of LINC00941 inhibits GC cells proliferation, migration, and invasion in vitro and modulates tumor growth in vivo. Our findings confirmed that LINC00941 plays an important oncogenic function in GC and may serve as a potential biomarker for diagnosis and prognosis of GC.
| S-EPMC6349697 | biostudies-literature
Project description:Background:Oral tongue squamous cell carcinoma (OTSCC) is an aggressive cancer which has high mortality rates. HOXA transcript at the distal tip (HOTTIP) is a lncRNA that can be used as a prognostic marker in multiple carcinomas. The expression of HOTTIP is found to be elevated in OTSCC tissues, and such elevation is correlated with poor prognosis. However, its functional role in regulating the growth and metastasis of OTSCC cells remains elusive and requires further investigation. Methods:HOTTIP-silenced OTSCC cells were established by inhibiting HOTTIP expression via its exclusive shRNA. Whether HOTTIP knockdown affected the aggressive tumor behaviors of OTSCC cells was investigated in vitro and in vivo. Results:We found that HOTTIP shRNA restrained the cell proliferation and arrested the cell cycle at G1 phase in TSCCA and TCA8113 cells. The expression levels of cyclins B, D1, and E were downregulated in HOTTIP-silenced cells. HOTTIP silencing suppressed the growth of xenograft tumors. Moreover, the silencing of HOTTIP triggered apoptosis in TSCCA and TCA8113 cells and altered the expression of a group of apoptosis-related molecules: downregulated Bcl-2, upregulated Bax, and enhanced the cleavage of caspase 3 and PARP. Knockdown of HOTTIP also suppressed the migration, invasion, and epithelial-mesenchymal transition (EMT) of both TSCCA and TCA8113 cell lines. Conclusion:Our findings suggest that HOTTIP is required by the OTSCC cells to maintain their growth and metastasis in vitro. It may serve as a promising potential candidate for OTSCC therapy.
| S-EPMC6239101 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) have recently emerged as vital players in tumor biology with potential value in cancer diagnosis, prognosis, and therapeutics. The lncRNA HULC (highly up-regulated in liver cancer) is increased in many malignancies, yet its serum expression profile and clinical value in gastric cancer (GC) patients remain unclear. Quantitative real-time polymerase chain reaction (RT-qPCR) for large-scale analysis of the serum expression of HULC in GC patients reliably detected circulating HULC and revealed that it is upregulated in GC patients. A high serum HULC level correlated with tumor size, lymph node metastasis, distant metastasis, tumor-node-metastasis stage, and H. pylori infection. The area under the ROC curve for HULC was up to 0.888, which was higher than that for CEA (0.694) and CA72-4 (0.514). Follow-up detection and Kaplan-Meier curve analysis revealed HULC is a good predictor of GC prognosis. Our present study indicates that circulating HULC may represent a novel serum tumor marker for early diagnosis and monitoring progression and prognosis of GC.
| S-EPMC5239513 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are involving in diverse cellular processes. However, their roles in reprogramming of gene expression profiles during lineage commitment and maturation of mesenchymal stem cells (MSCs) remain poorly understood. In the current study, we characterize the expression of a lncRNA, HoxA-AS3, during the differentiation of MSCs. We showed that HoxA-AS3 is increased upon adipogenic induction of MSCs, while HoxA-AS3 remains unaltered during osteogenic induction. Silencing of HoxA-AS3 in MSCs resulted in decreased adipogenesis and expression of adipogenic markers, PPARG, CEBPA, FABP4 and ADIPOQ. Conversely, knockdown of HoxA-AS3 expression in MSCs exhibited an enhanced osteogenesis and osteogenic markers expression, including RUNX2, SP7, COL1A1, IBSP, BGLAP and SPP1. Mechanistically, HoxA-AS3 interacts with Enhancer Of Zeste 2 (EZH2) and is required for H3 lysine-27 trimethylation (H3K27me3) of key osteogenic transcription factor Runx2. Our data reveal that HoxA-AS3 acts as an epigenetic switch that determines the lineage specification of MSC.
| S-EPMC5325385 | biostudies-literature
Project description:Background: Long non-coding RNAs (lncRNAs) are non-coding RNAs that have more than 200 nucleotides. They have recently emerged as important regulators of angiogenesis. To identify novel lncRNAs that may be involved in the regulation of angiogenesis, we detected the mRNA of 84 lncRNAs in human umbilical vein endothelial cells (HUVECs) exposed to hypoxia for 24h. One of these, rhabdomyosarcoma 2-associated transcript (RMST), is significantly upregulated by hypoxia. Little is known about the presence and roles of RMST in EC function. Objective: The main objective of the study was to investigate the regulation of RMST in ECs and to determine its role in EC survival, proliferation, migration, and differentiation. Methods: Using qPCR, basal mRNA levels of 10 RMST isoforms in HUVECs were measured. Levels were then measured in response to 24h of hypoxia, 7days of differentiation in a co-culture assay, and exposure to four different angiogenesis factors. Functional roles of RMST in EC survival, migration, and differentiation were quantified by using a loss-of-function approach (transfection with single-stranded antisense LNA GapmeRs). EC survival was measured using cell counts and crystal violet assays. Cell migration and differentiation were measured using scratch wound healing and Matrigel® differentiation assays, respectively. Results: Five RMST isoforms (RMST-202, -203, -204, -206, and -207) were detected in HUVECs and human microvascular endothelial cells (HMEC-1s). Other types of vascular cells, including human aortic valve interstitial cells and human aortic smooth muscle cells, did not display this expression profile. RMST was significantly upregulated in response to 24h of hypoxia and in response to 7days of HUVEC co-culture with human lung fibroblasts. RMST was significantly downregulated by angiopoietin-2 (Ang-2), but not by VEGF, FGF-2, or angiopoietin-1 (Ang-1). Selective knockdown of RMST demonstrated that it promotes EC survival in response to serum deprivation. It is also required for VEGF- and Ang-1-induced EC survival and migration, but not for differentiation. Conclusion: We conclude that RMST is expressed in human ECs and that this expression is upregulated in response to hypoxia and during differentiation into capillary-like structures. We also conclude that RMST plays important roles in EC survival and migration.
| S-EPMC8567064 | biostudies-literature
Project description:To investigate the expression patterns of long non-coding RNAs (lncRNAs) in gastric cancer.Two publicly available human exon arrays for gastric cancer and data for the corresponding normal tissue were downloaded from the Gene Expression Omnibus (GEO). We re-annotated the probes of the human exon arrays and retained the probes uniquely mapping to lncRNAs at the gene level. LncRNA expression profiles were generated by using robust multi-array average method in affymetrix power tools. The normalized data were then analyzed with a Bioconductor package linear models for microarray data and genes with adjusted P-values below 0.01 were considered differentially expressed. An independent data set was used to validate the results.With the computational pipeline established to re-annotate over 6.5 million probes of the Affymetrix Human Exon 1.0 ST array, we identified 136053 probes uniquely mapping to lncRNAs at the gene level. These probes correspond to 9294 lncRNAs, covering nearly 76% of the GENCODE lncRNA data set. By analyzing GSE27342 consisting of 80 paired gastric cancer and normal adjacent tissue samples, we identified 88 lncRNAs that were differentially expressed in gastric cancer, some of which have been reported to play a role in cancer, such as LINC00152, taurine upregulated 1, urothelial cancer associated 1, Pvt1 oncogene, small nucleolar RNA host gene 1 and LINC00261. In the validation data set GSE33335, 59% of these differentially expressed lncRNAs showed significant expression changes (adjusted P-value < 0.01) with the same direction.We identified a set of lncRNAs differentially expressed in gastric cancer, providing useful information for discovery of new biomarkers and therapeutic targets in gastric cancer.
| S-EPMC3691033 | biostudies-literature
Project description:Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are regarded as useful tools for cancer detection, particularly for the early stage; however, little is known about their diagnostic impact on gastric cancer (GC). We hypothesized that GC-related lncRNAs might release into the circulation during tumor initiation and could be utilized to detect and monitor GC. 8 lncRNAs which previously found to be differently expressed in GC were selected as candidate targets for subsequent circulating lncRNA assay. After validating in 20 pairs of tissues and plasma in training set, H19 was selected for further analysis in another 70 patients and 70 controls. Plasma level of H19 was significantly higher in GC patients compared with normal controls (p < 0.0001). By receiver operating characteristic curve (ROC) analysis, the area under the ROC curve (AUC) was 0.838; p < 0.001; sensitivity, 82.9%; specificity, 72.9%). Furthermore, H19 expression enabled the differentiation of early stage GC from controls with AUC of 0.877; sensitivity, 85.5%; specificity, 80.1%. Besides, plasma levels of H19 were significantly lower in postoperative samples than preoperative samples (p = 0.001). In conclusion, plasma H19 could serve as a potential biomarker for diagnosis of GC, in particular for early tumor screening.
| S-EPMC4476094 | biostudies-literature
Project description:Aim:Traditional non-invasive diagnostic markers for gastric cancer (GC) exhibit insufficient sensitivity and specificity. Circulating exosomes are clinically useful non-invasive biomarkers for tumor diagnosis. In addition to their potential role in cancer biology, circulating long non-coding RNAs (lncRNAs) are a new class of promising cancer biomarkers. In the present study, we aimed to identify lncRNAs in circulating exosomes with potential as biomarkers for GC detection. Methods:We compared the expression of CEBPA-AS1 between GC cells and gastric epithelial cells. The biological function of exosomal CEBPA-AS1 was determined by cell phenotype experiments and rescue assays. We also compared the expression of CEBPA-AS1 in cancerous tissue from GC patients and corresponding adjacent normal tissues, as well as the expression of CEBPA-AS1 in plasma exosomes of GC patients and healthy controls. Diagnostic accuracy was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results:CEBPA-AS1 was highly expressed in both GC cells and in exosomes secreted by GC cells. In addition, CEBPA-AS1-containing exosomes secreted by GC cells could promote cell proliferation and inhibit apoptosis, thereby inducing the malignant behavior of GC cells. The level of CEBPA-AS1 was also significantly increased in tissues and plasma exosomes of GC patients. Stability tests showed that most plasma CEBPA-AS1 was encased in exosomes, thus avoiding degradation by RNases. We evaluated the diagnostic accuracy of exosome-derived CEBPA-AS1. The AUC value of CEBPA-AS1 in discriminating GC patients from healthy controls was 0.824, which was higher than the diagnostic accuracy of other traditional tumor biomarkers. Conclusion:CEBPA-AS1-containing exosomes secreted from GC cells could promote cell proliferation, inhibit apoptosis, and induce GC progression, indicating that exosomal CEBPA-AS1 is involved in cell-to-cell communication in GC carcinogenesis. Exosomal CEBPA-AS1 is a promising new biomarker for clinical diagnosis of GC.
| S-EPMC7034294 | biostudies-literature
Project description:BACKGROUND Aberrant expression of long non-coding RNAs (lncRNAs) is associated with prognosis of gastric cancer, some of which could be further evaluated as potential biomarkers. In this study, we attempted to identify a specific lncRNA signature to predict the prognosis of gastric cancer. MATERIAL AND METHODS The genome-wide lncRNA expression in the high-throughput RNA-sequencing data was retrieved from the Cancer Genome Atlas (TCGA). Differential expression of lncRNAs was identified using the Limma package. Survival analysis was conducted by use of univariate and multivariate Cox regression models. Functional enrichment analysis of lncRNAs was based on co-expressed mRNAs. DAVID was used to perform gene ontology and KEGG pathway analysis. RESULTS A total of 452 differentially expressed lncRNAs between gastric cancer and matched normal tissues were screened, of which 76 lncRNAs were identified to be gastric cancer-specific from a pan-cancer analysis of 12 types of human cancer. Among these 76 gastric cancer-specific lncRNAs, 5 lncRNAs (CTD-2616J11.14, RP1-90G24.10, RP11-150O12.3, RP11-1149O23.2, and MLK7-AS1) were significantly associated with the overall survival of patients with gastric cancer. A gastric cancer-specific 5-lncRNA signature was deduced to divide the patients into high- and low-risk groups with significantly different survival times (P<0.0001). Multivariate Cox regression analysis showed that this 5-lncRNA signature was an independent predictor of prognosis. Functional enrichment analysis of the 5 lncRNAs showed that they were mainly involved in DNA replication, mitotic cell cycle, programmed cell death, and RNA splicing. CONCLUSIONS Our results suggest that this tumor-specific lncRNA signature may be clinically useful in the prediction of gastric cancer prognosis.
| S-EPMC5072383 | biostudies-literature
Project description:Gastric cancer (GC) is one of the major malignancies worldwide. Emerging evidence has revealed the potential involvement of long noncoding RNA (lncRNA) in human genetic disorders and cancer, but the role of LOC100505817 remains unknown. Thus, in this study, we isolated tissues from GC patients to characterize the functional importance of LOC100505817 in GC tumorigenesis. We also proposed a hypothesis that the regulation of Wnt/β-catenin pathway by LOC100505817 was regulated by miR-20a-mediated WT1. After the collection of cancer tissues and adjacent tissues were obtained from GC patients, expression of LOC100505817, Wnt/β-catenin pathway- and EMT-related genes was quantified. Ectopic expression and knockdown experiments were applied in order to investigate the protective role of LOC100505817 in the progression of GC. Subsequently, cell viability, flow cytometry for apoptosis and cell cycle were detected via CCK-8, while migration and invasion were determined using scratch test and Transwell assay respectively. Then interactions among LOC100505817, miR-20a and WT1 were explored by dual luciferase reporter gene assay, RNA pull down assay and RNA binding protein immunoprecipitation (RIP) assay. The results found poor expression LOC100505817 was poorly expressed in GC cells and tissues. Overexpressed LOC100505817 resulted in the significant reduction of cell proliferation, migration and invasion as well as the expression of Wnt2b, β-catenin, CyclinD1, N-cadherin, Vimentin and snail, while increased cell apoptosis along with the expression of E-cadherin. Wnt/β-catenin pathway and EMT in GC cells were suppressed by LOC100505817 through miR-20a-inhibted WT1. In summary, our results provided evidence suggesting that LOC100505817 inhibits GC through LOC100505817-mediated inhibition of Wnt/β-catenin pathway, that leads to the overall restraining of GC cell proliferation, migration and invasion through miR-20a-reduced WT1.
| S-EPMC8354317 | biostudies-literature