A competing endogenous RNA network identifies novel mRNA, miRNA and lncRNA markers for the prognosis of diabetic pancreatic cancer

Abstract

Pancreatic cancer (PaC) is highly associated with diabetes mellitus (DM). However, the mechanisms are insufficient. The study aimed to uncover the underlying regulatory mechanism on diabetic PaC and find novel biomarkers for the disease prognosis. Two RNA-sequencing (RNA-seq) datasets, GSE74629 and GSE15932, as well as relevant data in TCGA were utilized. After pretreatment, differentially expressed genes (DEGs) or miRNAs (DEMs) or lncRNAs (DELs) between diabetic PaC and non-diabetic PaC patients were identified, and further examined for their correlations with clinical information. Prognostic RNAs were selected using KM curve. Optimal gene set for classification of different samples were recognized by support vector machine. Protein-protein interaction (PPI) network was constructed for DEGs based on protein databases. Interactions among three kinds of RNAs were revealed in the 'lncRNA-miRNA-mRNA' competing endogenous RNA (ceRNA) network. A group of 32 feature genes were identified that could classify diabetic PaC from non-diabetic PaC, such as CCDC33, CTLA4 and MAP4K1. This classifier had a high accuracy on the prediction. Seven lncRNAs were tied up with prognosis of diabetic PaC, especially UCA1. In addition, crucial DEMs were selected, such as hsa-miR-214 (predicted targets: MAP4K1 and CCDC33) and hsa-miR-429 (predicted targets: CTLA4). Notably, interactions of 'HOTAIR-hsa-miR-214-CCDC33' and 'CECR7-hsa-miR-429-CTLA4' were highlighted in the ceRNA network. Several biomarkers were identified for diagnosis of diabetic PaC, such as HOTAIR, CECR7, UCA1, hsa-miR-214, hsa-miR-429, CCDC33 and CTLA4. 'HOTAIR-hsa-miR-214-CCDC33' and 'CECR7-hsa-miR-429-CTLA4' regulations might be two important mechanisms for the disease progression.

LINC00511 interacts with miR‐765 and modulates tongue squamous cell carcinoma progression by targeting LAMC2

“…The lncRNA‐miRNA‐mRNA regulatory network and the ceRNA mechanisms have been extensively confirmed in many reports, in which lncRNA competitively sponges miRNAs at post‐transcriptional level, thus leading to derepression of miRNA target genes . Based on the previous researches, we speculated that LINC00511 may also participate in the regulatory network of TSCC progression and own potential interactions with related miRNA.…”

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

“…System-level analysis is widely used to detect diseases. Recently, the ceRNA network has received substantial attention in various diseases, such as gastric cancer, colorectal cancer, and pancreatic cancer (13,35,36). However, research to date on ceRNA in DN is focused on a single lncRNA, a single miRNA, or an lncRNA-miRNA pair; there are no reports on the ceRNA network in DN.…”

lncRNA KIAA0125 functions as a tumor suppressor modulating growth and metastasis of colorectal cancer via Wnt/β‐catenin pathway

“…LncRNA KIAA0125 was found differentially expressed in many cancers (Yao et al, ; Diniz et al, ; Hornung et al, ). From our previous RNA‐sequencing bioinformatic analysis, lncRNA‐KIAA0125 was differentially expressed in several carcinomas (data unpublished).…”

“…The role of KIAA0125 in gallbladder cancer is not certainly defined because of the original related article was retracted (International BR, ). The bioinformatics analysis has shown KIAA0125 is downregulated in pancreatic cancer, but further investigations are required to elucidate the function (Yao et al, ). Therefore, the role of KIAA0125 in tumors may be cell‐type dependent, although this possibility needs to be further investigated.…”

“…The lncRNA KIAA0125 (on chromosome 14q32.33) was found aberrantly expressed and functionally involved in different cancers and diseases (Yao et al, ; Diniz et al, ; Hornung et al, ). However, its expression and function was never explored in CRC.…”