A Competing Endogenous RNA Network Reveals Novel Potential LncRNA, MiRNA, and MRNA Biomarkers in the Prognosis of Human Colon Adenocarcinoma

Background: Accumulating evidence indicated that long noncoding RNAs (lncRNAs) have a wide range of biological functions and may play significant roles in tumorigenesis and progression. However, the understanding of its functions and related competitive endogenous RNAs (ceRNAs) networks is much less than that of protein-coding genes, particularly in colon adenocarcinoma.

Methods: We comprehensively analyzed the sequencing data of protein-coding and noncoding RNAs in colon adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database. Next, we constructed colon adenocarcinoma-specific ceRNA network and evaluated the effect of these RNAs on overall survival (OS) for colon adenocarcinoma patients.

Results: Totally, 1138 differentially expressed lncRNAs (DElncRNAs), 245 microRNAs (DEmiRNAs), and 2081 mRNAs (DEmRNAs) were identified using a threshold of |logFoldChange| >2.0 and adjusted P-value < 0.01. Subsequently, a colon adenocarcinoma-specific ceRNA network was successfully established with133 DElncRNAs, 29 DEmiRNAs, and 55 DEmRNAs. Among ceRNA network, seven DElncRNAs (AL590483.1, AP004609.1, ARHGEF26-AS1, HOX transcript antisense RNA (HOTAIR), ITCH-IT1, KCNQ1OT1, and LINC00491), four DEmiRNAs (hsa-mir-143, hsa-mir-183, hsa-mir-216a, and hsa-mir-424), and six DEmRNAs (FJX1, TPM2, ULBP2, PDCD4, PLAU, and SERPINE1) significantly correlated with OS (all P-value < 0.05). Notably, several interactions were highlighted in the ceRNA network, such as "KCNQ1OT1-hsa-mir-183-PDCD4", "KCNQ1OT1-hsa-mir-424-TPM2", "HOTAIR-hsa-mir-143-SERPINE1", and "ARHGEF26-AS1-hsa-mir-143-SERPINE1".

Conclusions: These findings reveal several molecules might be novel important prognostic factors and potential treatment targets for colon adenocarcinoma. In addition, these observations contribute to a more comprehensive understanding of lncRNA-related ceRNA network and provide novel strategies for subsequent functional studies of lncRNAs in colon adenocarcinoma.