Analysis of lncRNA-Associated ceRNA Network Reveals Potential lncRNA Biomarkers in Human Colon Adenocarcinoma

Abstract

Background/Aims: Long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play significant roles in the development of tumors, but the functions of specific lncRNAs and lncRNA-related ceRNA networks have not been fully elucidated for colon adenocarcinoma (COAD). In this study, we aimed to clarify the lncRNA-microRNA (miRNA)-mRNA ceRNA network and potential lncRNA biomarkers in COAD. Methods: We extracted data from The Cancer Genome Atlas (TCGA) and identified COAD-specific mRNAs, miRNAs, and lncRNAs. The biological processes in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed for COAD-specific mRNAs. We then constructed a ceRNA network of COAD-specific mRNAs, miRNAs and lncRNAs and analyzed the correlation between expression patterns and clinical features of the lncRNAs involved. After identifying potential mRNA targets of 4 lncRNAs related to overall survival (OS), we conducted stepwise analysis of these targets through GO and KEGG. Using tissue samples from our own patients, we also verified certain analytical results using quantitative real-time PCR (qRT-PCR). Results: Data from 521 samples (480 tumor tissue and 41 adjacent non-tumor tissue samples) were extracted from TCGA. A total of 258 specific lncRNAs, 206 specific miRNAs, and 1467 specific mRNAs were identified (absolute log₂ [fold change] > 2, false discovery rate < 0.01). Analysis of KEGG revealed that specific mRNAs were enriched in cancer-related pathways. The ceRNA network was constructed with 64 lncRNAs, 18 miRNAs, and 42 mRNAs. Among these lncRNAs involved in the network, 3 lncRNAs (LINC00355, HULC, and IGF2-AS) were confirmed to be associated with certain clinical features and 4 lncRNAs (HOTAIR, LINC00355, KCNQ1OT1, and TSSC1-IT1) were found to be negatively linked to OS (log-rank p < 0.05). KEGG showed that the potential mRNA targets of these 4 lncRNAs may be concentrated in the MAPK pathway. Certain results were validated by qRT-PCR. Conclusion: This study providing novel insights into the lncRNA-miRNA-mRNA ceRNA network and reveals potential lncRNA biomarkers in COAD.

RNA sequencing reveals PNN and KCNQ1OT1 as predictive biomarkers of clinical outcome in stage III colorectal cancer patients treated with adjuvant chemotherapy

“…KCNQ1OT1 also reached statistical significance in the validation set after multivariate analysis. Higher expression levels of KCNQ1OT1 have been shown in tissues from solid tumors including colorectal cancer, and lung adenocarcinoma compared to normal mucosa. Interestingly, high mRNA expression levels of KCNQ1OT1 were correlated with paclitaxel resistance in lung cancer patients.…”

“…This epigenetic deregulation impacts the β‐catenin signaling and may contribute to the CRC development . Very recently, KCNQ1OT1 was shown to be negatively associated with OS in stages I–IV CRC patients . Our finding is the first that suggests a relationship between KCNQ1OT1 expression levels and DFS of stage III CRC patients treated with fluoropyrimidine‐based chemotherapy.…”

INHBA is a prognostic predictor for patients with colon adenocarcinoma

“…In China, the incidence and mortality of CRC rank fifth and fourth, respectively [3]. Colon adenocarcinoma is one of the most common types of CRC [4] and has become more prevalent in recent years [5]. Comprehensive treatment based on multidisciplinary discussion has become the trend of CRC treatment.…”

Identification of lncRNA biomarkers in lung squamous cell carcinoma using comprehensive analysis of lncRNA mediated ceRNA network

“…lncRNAs may play significant roles in varieties of biological functions during the tumorigenesis and metastasis of cancer [7]. In recent years, lncRNA-miRNA-mRNA ceRNA network has been demonstrated to involve in lung cancer [8], cervical squamous cell carcinoma [9], pancreatic adenocarcinoma [10], head and neck squamous carcinoma [11], breast cancer [12], colon adenocarcinoma [13], clear cell renal cell carcinoma [14], ovarian cancer [15], and so on. MiRNAs have been highly evolutionarily conserved and can interact with the target mRNA to silence the gene [16,17].…”