Identification of Novel Survival Related lncRNA-miRNA-mRNA Competing Endogenous RNA Network Associated with Immune Infiltration in Colorectal Cancer

Abstract

Background: Increasing studies have reported that long noncoding RNAs (lncRNAs) play critical roles in the initiation and progression of carcinogenesis. However, the underlying regulatory mechanisms of lncRNA related competing endogenous RNA (ceRNA) network in colorectal cancer (CRC) are not fully understood.Methods: Dysregulated microRNAs (miRNAs) in CRC samples were screened from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database. After that, the key miRNAs were filtered out through a comprehensive assessment of their expression levels and prognostic values. Subsequently, the targeted downstream mRNAs and upstream lncRNAs of the key miRNAs were predicted by using multiple bioinformatic databases. A ceRNA network was constructed by using Cytoscape, and the Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on this network using the DAVID database. Ultimately, expression levels and prognostic values of the lncRNAs and mRNAs were evaluated, and a survival related ceRNA network was constructed and visualized by using Cytoscape. In addition, the Gene Set Enrichment Analysis (GSEA) software package was employed to identify the pathways in which this survival related ceRNA network was enriched. Furthermore, correlations of ceRNA network with immune infiltration level were estimated by the Tumor Immune Estimation Resource (TIMER) databases.Results: In total, 28 dysregulated miRNAs were obtained, and two of them were identified as key miRNAs based on expression levels and prognostic values analyses. Subsequently, a total of three upstream lncRNAs and 309 downstream mRNAs were predicted by using bioinformatic tools, and two key lncRNAs and eight key mRNAs were identified by expression and survival analysis. A ceRNA regulatory network associated with the prognosis of CRC patients was constructed. Furthermore, GSEA analysis indicated the possible association of key mRNAs with CRC onset and progression. Importantly, immune infiltration analysis revealed that the ceRNA network was remarkably associated with infiltration abundance of multiple immune cells and expression levels of immune checkpoints.Conclusions: We constructed a survival related ceRNA regulatory network in human CRC, NEAT1 and XIST are potential prognostic factors that affect CRC onset and progression by targeting miR-195-5p.

WITHDRAWN: Investigating the miRNA of the Chinese herb Gecko on the cross-species regulation network of hepatocellular carcinoma

“…Research has demonstrated that miR-101 acts as a tumor suppressor by regulating abnormal NLK activity in the liver 41 . More interestingly, we also found that overexpression of miR-101 signi cantly inhibited proliferation, invasion, colony formation, and HCC progression in vivo by directly targeting the EZH2 oncogene 42 . This con rms the reliability of the Gecko miRNA regulatory network identi ed in our study.…”

Dihydroartemisinin inhibits HNSCC invasion and migration by controlling miR-195-5p expression

“…For example, the long non-coding RNA TRPM2 antisense RNA (TRPM2-AS) promotes invasion and migration of gastric cancer cells by suppressing miR-195/HMGA1 signaling axis [ 25 ]. Additionally, miR195-5p targets KIF23, inhibiting proliferation and migration in triple-negative breast cancer, as well as LITAF, which is related to colorectal cancer onset and progression [ 26 , 27 ]. These findings suggest that miR-195-5p has multiple target genes involved in the regulation of cell invasion and migration in different types of cancer.…”

Long Non-Coding RNAs in Colorectal Cancer: Navigating the Intersections of Immunity, Intercellular Communication, and Therapeutic Potential

“…Subsequent gene function scrutiny is conducted with the Database for Annotation, Visualization, and Integrated Discovery (DAVID), encompassing analyses like the KEGG Pathway and GO ontology. The validation phase involves the utilization of databases like the Gene Expression Profiling Interactive Analysis (GEPIA) and PrognoScan, culminating in the construction of an innovative regulatory network, an exploration via a Gene Set Enrichment Analysis (GSEA), and a correlation assessment with variables that are valuable for cancer biology or the clinic, such as immune infiltration levels [ 144 , 145 ]. Examples of the results of such studies include data published in the literature on RNA interactions that can influence various aspects of colorectal cancer biology, such as immune response and immune evasion, radioresistance and treatment response, tumor occurrence and metastasis, and probiotic- and pathobiont-related ceRNA networks; most of these play general roles as prognostic indicators.…”

“…Additional networks like CECR7-miR-206/miR-107, which may influence cytotoxic T cells and CRC invasion [ 150 ], and the ceRNA regulatory network involving NEAT1, XIST, and hsa-miR-195-5p [ 144 ], further exemplify how RNA networks are intertwined with immune responses in CRC. These interactions are significant for the infiltration of immune cells, such as CD4+/CD8+ T cells and macrophages, and immune escape in the CRC tumor microenvironment (TME).…”