MicroRNA-31-3p Is Involved in Substance P (SP)-Associated Inflammation in Human Colonic Epithelial Cells and Experimental Colitis

Abstract

Substance P (SP) mediates colitis. SP signaling regulates the expression of several miRNAs, including miR-31-3p, in human colonocytes. However, the role of miR-31-3p in colitis and the underlying mechanisms has not been elucidated. We performed real-time PCR analysis of miR-31-3p expression in human colonic epithelial cells overexpressing neurokinin-1 receptor (NCM460 NK-1R) in response to SP stimulation and in NCM460 cells after IL-6, IL8, tumor necrosis factor (TNF)-α, and interferon-γ exposure. Functions of miR-31-3p were tested in NCM460-NK-1R cells and the trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) models of colitis. Targets of miRNA-31-3p were confirmed by Western blot analysis and luciferase reporter assay. Jun N-terminal kinase inhibition decreased SP-induced miR-31-3p expression. miR-31-3p expression was increased in both TNBS- and DSS-induced colitis and human colonic biopsies from ulcerative colitis, compared with controls. Intracolonic administration of a miR-31-3p chemical inhibitor exacerbated TNBS- and DSS-induced colitis and increased colonic TNF-α, CXCL10, and chemokine (C-C motif) ligand 2 (CCL2) mRNA expression. Conversely, overexpression of miR-31-3p ameliorated the severity of DSS-induced colitis. Bioinformatic, luciferase reporter assay, and Western blot analyses identified RhoA as a target of miR-31-3p in NCM460 cells. Constitutive activation of RhoA led to increased expression of CCL2, IL6, TNF-α, and CXCL10 in NCM460-NK-1R cells on SP stimulation. Our results reveal a novel SP-miR-31-3p-RhoA pathway that protects from colitis. The use of miR-31-3p mimics may be a promising approach for colitis treatment.

miR-31-3p Expression and Benefit from Anti-EGFR Inhibitors in Metastatic Colorectal Cancer Patients Enrolled in the Prospective Phase II PROSPECT-C Trial

“…Cetuximab is known to trigger intratumor inflammatory infiltration in liver metastases, with an enrichment of CD3 À , CD8 À , and CD56 þ cells (37). Given miR-31-3p is also involved in immune and inflammatory cells homeostasis (38)(39)(40)(41), its overexpression might sometimes be due to intratumor infiltration from lymphocites or inflammatory cells. Under these circumastances, despite tissue microdissection, contamination by inflammatory cells might potentially lead to a bias in miR-31-3p scoring when using high sensitivity RT-PCR-based assays.…”

TGFBR2‑dependent alterations of microRNA profiles in extracellular vesicles and parental colorectal cancer cells

“…Therefore, it was hypothesized that high levels of miR-4521-3p may favor the inflammatory environment often observed in MSI tumors. The second candidate found to be upregulated in dT cells, miR-31-3p, has also been associated with intestinal inflammation (62). Olaru et al suggested that the expression of miR-31-3p increases during the progression of inflammation-associated intestinal neoplasia (63).…”

Substance P induces sympathetic immune response in the contralateral eye after the first eye cataract surgery in type 2 diabetic patients

“…MCP-1, also called chemokine (C-C motif) ligand 2 (CCL2), is a pain-related inflammatory cytokine that recruits several types of immune cells to the sites of inflammation in the condition of tissue injury or infection [9]. MCP-1 production could be regulated by SP concentrations in different cell types [10][11][12], indicating that SP can stimulate MCP-1 production which attracts inflammatory cells to specific sites. The previous studies focused on the changes of the pain-related inflammatory cytokines such as interleukin (IL)-1, IL-6,12 IL-8, spinal macrophage inflammatory protein (MIP), MCP-1, vascular endothelial growth factor (VEGF), and regulated on activation, normal T expressed and secreted (RANTES) before and after cataract surgery of the first eye, however the neuropeptide SP has not been identified.…”