Dataset Information

Identification and Development of Long Non-coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma.

ABSTRACT: Background and aims: Pancreatic adenocarcinoma (PAAD) is the most lethal cancer type around the world. With the in-depth exploration of the function of long non-coding RNAs (lncRNAs), the competing endogenous RNA (ceRNA) mechanism has shown its potential to partially reveal the pathogenesis of PAAD. This study aimed to construct a lncRNA-associated ceRNA network and explore ceRNA regulatory axes with experimental and prognostic value in PAAD.

Methods: First, we applied differential expression analysis in the TCGA_PAAD dataset. Then, interaction analysis and survival analysis in multiple RNA interaction databases were conducted to construct a ceRNA network. Finally, a potential regulatory axis was validated using clinical samples and cell lines by quantitative realtime PCR (qRT-PCR).

Results: A ceRNA network comprising 13 lncRNAs, 96 miRNAs, and 30 mRNAs was successfully constructed. Survival analysis further narrowed this network to five lncRNAs, three miRNAs, and seven mRNAs, which were significantly associated with patients' overall survival. A potential regulatory axis CASC8-miR-129-5p-TOB1 was further experimentally validated. The expression of these genes was associated with clinicopathological factors and their expression trend was consistent with ceRNA mechanism. Specifically, knockdown of lncRNA-CASC8 led to the overexpression of miR-129-5p and down-regulation of TOB1, while overexpression of CASC8 showed opposite effects.

Conclusion: This novel ceRNA regulatory network could provide new insight into the pathogenesis of PAAD. The new regulatory axis CASC8-miR-129-5p-TOB1 might serve as a potential therapeutic target for patients.

SUBMITTER: Zhu W

PROVIDER: S-EPMC7699307 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Identification and Development of Long Non-coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma.

Zhu Wenjuan W Gao Wenzhe W Deng Yanyao Y Yu Xiao X Zhu Hongwei H

OncoTargets and therapy 20201123

<h4>Background and aims</h4>Pancreatic adenocarcinoma (PAAD) is the most lethal cancer type around the world. With the in-depth exploration of the function of long non-coding RNAs (lncRNAs), the competing endogenous RNA (ceRNA) mechanism has shown its potential to partially reveal the pathogenesis of PAAD. This study aimed to construct a lncRNA-associated ceRNA network and explore ceRNA regulatory axes with experimental and prognostic value in PAAD.<h4>Methods</h4>First, we applied differential ...[more]

PMID: 33262608

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Project description:Background:The aim of this study was to investigate the regulatory network of lncRNAs as competing endogenous RNAs (ceRNA) in bladder urothelial carcinoma (BUC) based on gene expression data derived from The Cancer Genome Atlas (TCGA). Materials and methods:RNA sequence profiles and clinical information from 414 BUC tissues and 19 non-tumor adjacent tissues were downloaded from TCGA. Differentially expressed RNAs derived from BUC and non-tumor adjacent samples were identified using the R package "edgeR". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using the "clusterProfiler" package. Gene ontology and protein-protein interaction (PPI) networks were analyzed for the differentially expressed mRNAs using the "STRING" database. The network for the dysregulated lncRNA associated ceRNAs was then constructed for BUC using miRcode, miRTarBase, miRDB, and TargetScan. Cox regression analysis was performed to identify independent prognostic RNAs associated with BUC overall survival (OS). Survival analysis for the independent prognostic RNAs within the ceRNA network was calculated using Kaplan-Meier curves. Results:Based on our analysis, a total of 666, 1819 and 157 differentially expressed lncRNAs, mRNAs and miRNAs were identified respectively. The ceRNA network was then constructed and contained 59 lncRNAs, 23 DEmiRNAs, and 52 DEmRNAs. In total, 5 lncRNAs (HCG22, ADAMTS9-AS1, ADAMTS9-AS2, AC078778.1, and AC112721.1), 2 miRNAs (hsa-mir-145 and hsa-mir-141) and 6 mRNAs (ZEB1, TMEM100, MAP1B, DUSP2, JUN, and AIFM3) were found to be related to OS. Two lncRNAs (ADAMTS9-AS1 and ADAMTS9-AS2) and 4 mRNA (DUSP2, JUN, MAP1B, and TMEM100) were validated using GEPIA. Thirty key hub genes were identified using the ranking method of degree. KEGG analysis demonstrated that the majority of the DEmRNAs were involved in pathways associated with cancer. Conclusion:Our findings provide an understanding of the important role of lncRNA-related ceRNAs in BUC. Additional experimental and clinical validations are required to support our findings.

Project description:Hox transcript antisense RNA (HOTAIR) is a long non-coding RNA (lncRNA) that serves a key role in the pathogenesis of various types of cancer, including pancreatic adenocarcinoma. However, the diagnostic and prognostic values of HOTAIR in pancreatic adenocarcinoma, as well as its involvement in cancer cell energy metabolism, remain unclear. In the present study, tumor tissues and adjacent healthy tissues were collected from patients with pancreatic adenocarcinoma, and blood samples were collected from patients and healthy controls. Expression levels of HOTAIR and hexokinase-2 (HK2) were detected by reverse transcription-quantitative polymerase chain reaction. All patients were followed up for 5 years, and the diagnostic and prognostic values of serum HOTAIR levels were investigated by receiver operating characteristic curve and survival analyses, respectively. Pancreatic adenocarcinoma cell lines overexpressing HOTAIR and HK2 were established, and the effects on cell proliferation, lactate production, glucose uptake and ATP production were detected by Cell Counting Kit-8, lactate, glucose uptake and ATP assays, respectively. The protein expression was detected by western blot analysis. The results revealed that HOTAIR and HK2 expression levels were increased in tumor tissues compared with adjacent healthy tissues. The serum levels of HOTAIR and HK2 were higher in patients with pancreatic cancer compared with healthy controls. The serum levels of these two factors may be used to accurately predict pancreatic adenocarcinoma and its prognosis. HOTAIR and HK2 overexpression led to the promotion of tumor cell proliferation. HOTAIR overexpression increased lactate production, glucose uptake and ATP production. Furthermore, it promoted HK2 expression, however HK2 overexpression displayed no significant effects on HOTAIR expression levels. Therefore, it was concluded that the lncRNA HOTAIR may promote cancer cell energy metabolism in pancreatic adenocarcinoma by upregulating HK2.

Dataset Information

Identification and Development of Long Non-coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma.

Publications

Identification and Development of Long Non-coding RNA Associated Regulatory Network in Pancreatic Adenocarcinoma.

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