Background: Competing endogenous RNA (ceRNA) represents a class of RNAs (e.g., long noncoding RNAs [lncRNAs]) with microRNA (miRNA) binding sites, which can competitively bind miRNA and inhibit its regulation of target genes. Increasing evidence has underscored the involvement of dysregulated ceRNA networks in the occurrence and progression of colorectal cancer (CRC). The purpose of this study was to construct a ceRNA network related to the prognosis of CRC and further explore the potential mechanisms that affect this prognosis. Methods: RNA-Seq and miRNA-Seq data from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed lncRNAs (DElncRNAs), microRNAs (DEmiRNAs), and mRNAs (DEmRNAs), and a prognosis-related ceRNA network was constructed based on DElncRNA survival analysis. Subsequently, pathway enrichment, Pearson correlation, and Gene Set Enrichment Analysis (GSEA) were performed to determine the function of the genes in the ceRNA network. Gene Expression Profiling Interactive Analysis (GEPIA) and immunohistochemistry (IHC) were also used to validate differential gene expression. Finally, the correlation between lncRNA and immune cell infiltration in the tumor microenvironment was evaluated based on the CIBERSORT algorithm. Results: A prognostic ceRNA network was constructed with eleven key survival-related DElncRNAs (MIR4435-2HG, NKILA, AFAP1-AS1, ELFN1-AS1, AC005520.2, AC245884.8, AL354836.1, AL355987.4, AL591845.1, LINC02038, and AC104823.1), 54 DEmiRNAs, and 308 DEmRNAs. The MIR4435-2HG- and ELFN1-AS1-associated ceRNA subnetworks affected and regulated the expression of the COL5A2, LOX, OSBPL3, PLAU, VCAN, SRM, and E2F1 target genes and were found to be related to prognosis and tumor-infiltrating immune cell types. Conclusions: MIR4435-2HG and ELFN1-AS1 are associated with prognosis and tumor-infiltrating immune cell types and could represent potential prognostic biomarkers or therapeutic targets in colorectal carcinoma.

The pathogenesis of inflammatory bowel disease (IBD) is still unknown. Mesenteric lymphatics (MLs), which are closely related to the intestine in both anatomy and physiology, have been suggested to be involved in IBD. In the present study, we aim to investigate the effects of ML immune cells on IBD and explore the potential associated mechanisms. Acute colitis was induced in rats using dextran sulfate sodium salt (DSS). Mesenteric lymphangiogenesis, ML stenosis, and dilation were observed, with an increased proportion of MLB cells in DSS-induced colitis rats. The adoptive transfer of B cells isolated from ML (MLB) was employed to investigate their effects on colitis. MLB cells derived from DSS-induced colitis rats exhibited a higher propensity to migrate to the intestine. The proportion of colonic T cells was altered, along with the aggravated colitis induced by the adoptive transfer of MLB cells derived from DSS-induced colitis rats. RNA sequencing revealed increased Cxcr5 expression in MLB cells from colitis rats, while real-time PCR indicated an upregulation of its ligand Cxcl13 in the colon of colitis rats. These findings suggest that MLB cells may migrate to the intestine and aggravate colitis. In summary, colonic T cells respond to MLB cells from colitis rats, and MLB cells aggravate DSS-induced colitis via the CXCR5–CXCL13 axis.

Inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC), is affecting a growing global population. Unlike UC, which is characterized by inflammation confined to the intestinal mucosa and submucosa, CD involves transmural inflammation of the intestine. Although the lymphatic system is believed to play a role in the pathogenesis of CD, its exact contribution remains poorly understood. Mesenteric lymphatics (MLs), which drain interstitial fluid and immune cells into mesenteric lymph nodes, have been implicated in this process. In the present study, we aimed to investigate the role of ML immune cells in TNBS-induced colitis in rats. Flow cytometry analysis revealed an increased ratio of B cells and altered B cell function in the MLs of colitis rats compared to controls. The adoptive transfer of mesenteric lymphatic B (MLB) cells isolated from colitis rats to recipient rats exacerbated colitis and was associated with the enhanced migration of MLB cells to the gut. RNA sequencing analysis demonstrated a significant upregulation of genes associated with inflammation and immune responses in MLB cells from colitis rats, particularly key molecules involved in T cell activation, such as cluster of differentiation 27 (Cd27) and cluster of differentiation 40 (Cd40), and the chemotactic receptor C-C motif chemokine receptor 8 (Ccr8), which mediates B cell migration in response to T cells. Mechanistically, MLB cells from colitis rats were recruited to the colon by intra-intestinal T cells through the Ccr8-C-C motif chemokine ligand 1 (Ccl1) axis, where they subsequently exacerbated inflammatory responses via enhanced differentiation. These observations indicate that the migration of MLB cells to the gut exacerbates TNBS-induced colitis in rats by modulating intestinal T cells.