Comprehensive analysis of lncRNA‑associated ceRNA network reveals the novel potential of lncRNA, miRNA and mRNA biomarkers in human rectosigmoid junction cancer

Abstract

Although accumulating evidence has confirmed the potential biological functions of long non-coding RNAs (lncRNAs) as competitive endogenous RNAs (ceRNAs) in colorectal tumorigenesis and progression, few studies have focused on rectosigmoid junction cancer. In the present study, a comprehensive analysis was conducted to explore lncRNA-mediated ceRNA implications and their potential value for prognosis. lncRNA, microRNA (miR/miRNA) and mRNA expression profiles were downloaded from The Cancer Genome Atlas database. Subsequently, a lncRNA-miRNA-mRNA regulatory network was constructed to evaluate the functions of these differentially expressed genes on overall survival (OS) for rectosigmoid junction cancer. As a result, a rectosigmoid junction cancer-specific ceRNA network was successfully constructed with 7 differentially expressed (DE)lncRNAs, 16 DEmiRNAs and 71 DEmRNAs. Among the network, one DElncRNA (small nucleolar RNA host gene 20) and three mRNAs (sodium- and chloride-dependent taurine transporter, fibroblast growth factor 13 and tubulin polyglutamylase TTLL7) were significantly associated with OS (P<0.05). Additionally, two lncRNAs (KCNQ1OT1 and MIR17HG) interacted with most of the DEmiRNAs. Notably, two top-ranked miRNAs (hsa-miR-374a-5p and hsa-miR-374b-5p) associated networks were identified to be markedly associated with the pathogenesis. Furthermore, four DEmRNAs (caveolin-1, MET, filamin-A and AKT3) were enriched in the Kyoto Encylopedia of Gene and Genomes pathway analysis, as well as being included in the ceRNA network. In summary, the present results revealed that a specific lncRNA-miRNA-mRNA network was associated with rectosigmoid junction cancer, providing several molecules that may be used as novel prognostic biomarkers and therapeutic targets.

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer

“…Park et al reported that the clinicopathological characteristics of the rectosigmoid junction cancer are similar to those of sigmoid or rectal cancer, but the rectosigmoid junction cancer has different patterns of lymphatic spread compared to the sigmoid colon or rectum cancer and more frequently metastasizes to the pararectal nodes ( 13 ). The distinctive RNA network of the rectosigmoid junction has also been reported ( 21 , 22 ). A recent study reported that the rectosigmoid junction had a deviant behavioral pattern compared to the patterns of adjacent bowel segments, including lower 5-year overall survival and higher lymph vascular invasion ( 35 ).…”

“…A previous study also revealed that the sigmoid-rectal region appears to have unique molecular features compared to those of other colon-sided locations ( 20 ). The distinctive competing endogenous RNA and long non-coding RNAs of the rectosigmoid junction cancer have been reported ( 21 , 22 ). A multi-omics study of gastric cancer has also demonstrated the heterogeneity of molecular features ( 23 ).…”

Integrating molecular pathway with genome-wide association data for causality identification in breast cancer

“…Subsequently, if all four databases concur on a specific miRNA as a potential target, it is retained as the designated targeted miRNA [ 28 ]. Additionally, we utilized the spongeScan database to anticipate the lncRNAs that target the binding of miRNAs and assigned names to the identified targeted lncRNAs [ 29 ]. Lastly, to depict the regulatory network involving circRNA-miRNA-mRNA, we employed Cytoscape software for visualization purposes.…”

The ceRNA network regulates epithelial-mesenchymal transition in colorectal cancer

“…MiRNAs bind to partially complementary sequences of target gene transcription products, which are known as response elements (MREs). Endogenous RNA with the same MREs can competitively bind to miRNA, which is called competitive endogenous RNA (ceRNA) [ 7 , 8 ]. LncRNAs, cirRNAs, and pseudogenes can compete with miRNA for the same miRNA response elements and reduce miRNA inhibition, increasing the expression of miRNA target genes (mRNA) [ 7 , [9] , [10] , [11] ].…”

“…Endogenous RNA with the same MREs can competitively bind to miRNA, which is called competitive endogenous RNA (ceRNA) [ 7 , 8 ]. LncRNAs, cirRNAs, and pseudogenes can compete with miRNA for the same miRNA response elements and reduce miRNA inhibition, increasing the expression of miRNA target genes (mRNA) [ 7 , [9] , [10] , [11] ]. CeRNA is a novel regulatory mechanism in cancer, which is attracting widespread attention and is involved in many biological processes, including epithelial-mesenchymal transition (EMT), proliferation, apoptosis, metastasis, and chemoresistance [ 12 , 13 ].…”