Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LncRNAs and Esophageal Squamous Cell Carcinoma - Implications for Pathogenesis and Drug Development.

ABSTRACT: LncRNAs are a group of ncRNA species longer than 200 nt, which have fundamental regulatory roles in diverse cellular processes and diseases progression. Esophageal cancer is a serious malignancy with respect to prognosis and mortality rate. It is among the five leading cancer types for the cancer deaths in males of middle age in the United States. In China, esophageal cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death. The molecular mechanisms of esophageal cancer development are not fully understood, but emerging studies point out that lncRNAs may actively associate with the pathogenesis. In this review, we first provided an introduction of lncRNAs classifications. Then we focused on the recent findings on lncRNA expression and function in esophageal cancer development. Implications for pathogenesis and potential drug developments will also be discussed.

SUBMITTER: Shen WJ

PROVIDER: S-EPMC4934034 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

LncRNAs and Esophageal Squamous Cell Carcinoma - Implications for Pathogenesis and Drug Development.

Shen Wen-Jun WJ Zhang Fan F Zhao Xing X Xu Jianzhen J

Journal of Cancer 20160623 10

LncRNAs are a group of ncRNA species longer than 200 nt, which have fundamental regulatory roles in diverse cellular processes and diseases progression. Esophageal cancer is a serious malignancy with respect to prognosis and mortality rate. It is among the five leading cancer types for the cancer deaths in males of middle age in the United States. In China, esophageal cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death. The molecular mechanisms of e ...[more]

PMID: 27390601

Similar Datasets

Prognostic value and immune landscapes of cuproptosis-related lncRNAs in esophageal squamous cell carcinoma.

Project description:BackgroundPrecisely forecasting the prognosis of esophageal squamous cell carcinoma (ESCC) patients is a formidable challenge. Cuproptosis has been implicated in ESCC pathogenesis; however, the prognostic value of cuproptosis-associated long noncoding RNAs (CuRLs) in ESCC is unclear.MethodsTranscriptomic and clinical data related to ESCC were sourced from The Cancer Genome Atlas (TCGA). Using coexpression and Cox regression analysis to identify prognostically significant CuRLs, a prognostic signature was created. Nomogram models were established by incorporating the risk score and clinical characteristics. Tumor Immune Dysfunction and Rejection (TIDE) scores were derived by conducting an immune landscape analysis and evaluating the tumor mutational burden (TMB). Drug sensitivity analysis was performed to explore the underlying molecular mechanisms and guide clinical dosing.ResultsOur risk score based on 5 CuRLs accurately predicted poorer prognosis in high-risk ESCC patients across almost all subgroups. The nomogram that included the risk score provided more precise prognostic predictions. Immune pathways, such as the B-cell receptor signaling pathway, were enriched in the datasets from high-risk patients. High TMB in high-risk patients indicated a relatively poor prognosis. High-risk patients with lower TIDE scores were found to benefit more from immunotherapy. High-risk patients exhibited greater responsiveness to Nilotinib, BI-2536, P22077, Zoledronate, and Fulvestrant, as revealed by drug sensitivity analysis. Real-time PCR validation demonstrated significant differential expression of four CuRLs between ESCC and normal cell lines.ConclusionsThe above risk score and nomogram can accurately predict prognosis in ESCC patients and provide guidance for chemotherapy and immunotherapy.

| S-EPMC10599721 | biostudies-literature

Risk Stratification and Validation of Eleven Autophagy-Related lncRNAs for Esophageal Squamous Cell Carcinoma.

Project description:Esophageal squamous cell carcinoma (ESCC), the most prevalent subtype of esophageal cancer, ranks sixth in cancer-related mortality, making it one of the deadliest cancers worldwide. The identification of potential risk factors for ESCC might help in implementing precision therapies. Autophagy-related lncRNAs are a group of non-coding RNAs that perform critical functions in the tumor immune microenvironment and therapeutic response. Therefore, we aimed to establish a risk model composed of autophagy-related lncRNAs that can serve as a potential biomarker for ESCC risk stratification. Using the RNA expression profile from 179 patients in the GSE53622 and GSE53624 datasets, we found 11 lncRNAs (AC004690.2, AC092159.3, AC093627.4, AL078604.2, BDNF-AS, HAND2-AS1, LINC00410, LINC00588, PSMD6-AS2, ZEB1-AS1, and LINC02586) that were co-expressed with autophagy genes and were independent prognostic factors in multivariate Cox regression analysis. The risk model was constructed using these autophagy-related lncRNAs, and the area under the receiver operating characteristic curve (AUC) of the risk model was 0.728. To confirm that the model is reliable, the data of 174 patients from The Cancer Genome Atlas (TCGA) esophageal cancer dataset were analyzed as the testing set. A nomogram for ESCC prognosis was developed using the risk model and clinic-pathological characteristics. Immune function annotation and tumor mutational burden of the two risk groups were analyzed and the high-risk group displayed higher sensitivity in chemotherapy and immunotherapy. Expression of differentially expressed lncRNAs were further validated in human normal esophageal cells and esophageal cancer cells. The constructed lncRNA risk model provides a useful tool for stratifying risk and predicting the prognosis of patients with ESCC, and might provide novel targets for ESCC treatment.

| S-EPMC9271611 | biostudies-literature

Integrative analyses of transcriptome sequencing identify novel functional lncRNAs in esophageal squamous cell carcinoma.

Project description:Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.

| S-EPMC5337622 | biostudies-literature

Molecular Deregulation of EPAS1 in the Pathogenesis of Esophageal Squamous Cell Carcinoma.

Project description:Endothelial PAS domain-containing protein 1 (EPAS1) is an angiogenic factor and its implications have been reported in many cancers but not in esophageal squamous cell carcinoma (ESCC). Herein, we aim to examine the genetic and molecular alterations, clinical implications, and functional roles of EPAS1 in ESCC. High-resolution melt-curve analysis and Sanger sequencing were used to detect mutations in EPAS1 sequence. EPAS1 DNA number changes and mRNA expressions were analyzed by polymerase chain reaction. in vitro functional assays were used to study the impact of EPAS1 on cellular behaviors. Overall, 7.5% (n = 6/80) of patients with ESCC had mutations in EPAS1, and eight novel variants (c.1084C>T, c.1099C>A, c.1145_1145delT, c.1093C>G, c.1121T>G, c.1137_1137delG, c.1135_1136insT, and c.1091_1092insT) were detected. Among these mutations, four were frameshift (V382Gfs*12, A381Lfs*13, K379Ifs*6, and K364Nfs*12) mutations and showed the potential of non-sense-mediated mRNA decay (NMD) in computational analysis. The majority of patients showed molecular deregulation of EPAS1 [45% (n = 36/80) DNA amplification, 42.5% (n = 34/80) DNA deletion, as well as 53.7% (n = 43/80) high mRNA expression, 20% (n = 16/80) low mRNA expression]. These alterations of EPAS1 were associated with tumor location and T stages. Patients with stage III ESCC having EPAS1 DNA amplification had poorer survival rates in comparison to EPAS1 DNA deletion (p = 0.04). In addition, suppression of EPAS1 in ESCC cells showed reduced proliferation, wound healing, migration, and invasion in comparison to that of control cells. Thus, the molecular and functional studies implied that EPAS1 plays crucial roles in the pathogenesis of ESCC and has the potential to be used as a prognostic marker and as a therapeutic target.

| S-EPMC7518048 | biostudies-literature

JMJD3 promotes esophageal squamous cell carcinoma pathogenesis through epigenetic regulation of MYC.

Project description: Not available

| S-EPMC7447641 | biostudies-literature

EI24 Inhibits Cell Proliferation and Drug Resistance of Esophageal Squamous Cell Carcinoma.

Project description:Drug resistance, whether intrinsic or acquired, often leads to treatment failure in esophageal squamous cell carcinoma (ESCC). Clarifying the mechanism of drug resistance in ESCC has great significance for reversing drug resistance, as well as improving the prognosis of patients. Previously, we demonstrated that etoposide-induced 2.4-kb mRNA (EI24) is the target of miR-483-3p, which promoted the growth, migration, and drug resistance in ESCC, suggesting that EI24 participates in repressing the tumorigenesis and progression of ESCC. Here, we observed that EI24 was remarkably decreased in ESCC tissues. Moreover, its expression was directly linked to the prognosis of patients. We then confirmed that the forced overexpression of EI24 repressed cell growth and sensitized ESCC cells to chemotherapeutic agents, whereas EI24 silencing had the opposite effect. Furthermore, gene microarray and ingenuity pathway analysis (IPA) were performed to establish the potential mechanisms and indicated that EI24 exerts a tumor-suppressive role via suppressing the acute phase response signaling pathway or IL-1 signaling pathway in ESCC. Collectively, our data reveal that EI24 overexpression attenuates malignant phenotypes of ESCC and that it is a novel possible ESCC therapeutic target.

| S-EPMC7471874 | biostudies-literature

Aberrant DNA Methylation in Esophageal Squamous Cell Carcinoma: Biological and Clinical Implications.

Project description:Almost all cancer cells possess multiple epigenetic abnormalities, which cooperate with genetic alterations to enable the acquisition of cancer hallmarks during tumorigenesis. As the most frequently found epigenetic change in human cancers, aberrant DNA methylation manifests at two major forms: global genomic DNA hypomethylation and locus-specific promoter region hypermethylation. It has been recognized as a critical contributor to esophageal squamous cell carcinoma (ESCC) malignant transformation. In ESCC, DNA methylation alterations affect genes involved in cell cycle regulation, DNA damage repair, and cancer-related signaling pathways. Aberrant DNA methylation patterns occur not only in ESCC tumors but also in precursor lesions. It adds another layer of complexity to the ESCC heterogeneity and may serve as early diagnostic, prognostic, and chemo-sensitive markers. Characterization of the DNA methylome in ESCC could help better understand its pathogenesis and develop improved therapies. We herein summarize the current research and knowledge about DNA methylation in ESCC and its clinical significance in diagnosis, prognosis, and treatment.

| S-EPMC7645039 | biostudies-literature

Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients.

Project description:Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. The exomes of more than 600 ESCCs have been sequenced in the past 4 years, and numerous key aberrations have been identified. Recently, researchers reported both inter- and intratumor heterogeneity. Although these are interesting observations, their clinical implications are unclear due to the limited number of samples profiled. Epigenomic alterations, such as changes in DNA methylation, histone acetylation, and RNA editing, also have been observed in ESCCs. However, it is not clear what proportion of ESCC cells carry these epigenomic aberrations or how they contribute to tumor development. We review the genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes. We discuss their clinical implications and future research directions.

| S-EPMC5951382 | biostudies-literature

Immunotherapy for Esophageal Squamous Cell Carcinoma.

Project description:Esophageal squamous cell carcinoma have been frustrating to treat, with slow progress made on extending survival. Immunotherapy targeting immune checkpoints, T cells, and infiltrating lymphocytes has shown promise in early studies. The efficacy of pembrolizumab and nivolumab is encouraging. Anti-chemokine receptors and oncolytic viruses are also making headway against these stubborn tumors; improved results when immune checkpoint inhibitors are combined with radiation therapy are eagerly anticipated. Adoptive T cell therapy and vaccines are also under development. The importance of a multidisciplinary approach cannot be emphasized enough.

| S-EPMC5374168 | biostudies-literature

Stemness and chemotherapeutic drug resistance induced by EIF5A2 overexpression in esophageal squamous cell carcinoma.

Project description:Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients' drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy (P < 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.

| S-EPMC4694887 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data