MicroRNA‑139‑5p regulates chronic inflammation by suppressing nuclear factor‑κB activity to inhibit cell proliferation and invasion in colorectal cancer

Abstract

The inflammatory microenvironment, which mediates the initiation and malignant development of tumors, has been reported to be associated with microRNA (miRNA) dysregulation. In the present study, the expression of miR-139-5p was analyzed in colorectal cancer (CRC) cell lines SW480, HT29, HCT-8, LoVo and HCT116, aiming to investigate the function and mechanism of miR-139-5p in the regulation of the malignant phenotypes of CRC. miR-139-5p expression was found to be considerably downregulated in CRC cell lines compared with the human normal colon mucosal epithelial cell line NCM460. Subsequently, it was demonstrated that overexpression of miR-139-5p in colon cancer cell lines significantly suppressed the cell proliferation in vitro and in vivo. In addition, overexpression of miR-139-5p further inhibited the invasion ability of colon cancer cells in vitro, concomitantly with downregulation of key invasion-associated proteins, including matrix metalloproteinase 9 (MMP9) and MMP7. Furthermore, it was demonstrated that overexpression of miR-139-5p decreased the expression levels of inflammatory cytokines, including interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), by suppressing nuclear factor (NF)-κB activity. Therefore, these findings collectively indicated that miR-139-5p regulated chronic inflammation by suppressing NF-κB activity in order to inhibit cell proliferation and invasion in CRC, thereby indicating a novel molecular mechanism in CRC therapy.

Enhancer of zeste homolog 2 participates in the process of atherosclerosis by modulating microRNA‐139‐5p methylation and signal transducer and activator of transcription 1 expression

“…34 Furthermore, a recent study has revealed that overexpressed miR-139-5p reduces the inflammatory cytokines expression. 36 The observation of the study was that reduced EZH2 or elevated miR-139-5p accelerated cell proliferation and suppressed apoptosis of HASMCs, restrained oxidative stress and cell apoptosis in arterial tissues of mice with AS. This finding is also reported by Zhang et al that repressive EZH2 also inhibits the progression of lung injury by declining the pulmonary cell apoptosis.…”

“…37 Moreover, the finding is persistent with that of Zhu et al who demonstrates that excessive miR-139-5p in colon cancer cell lines obviously suppresses the cell proliferation in vitro and in vivo. 36 Another study has elucidated that all types of gain-of-function assays exhibits that the up-regulated miR-139-5p represses cell proliferation and induces cell apoptosis. 38 In conclusion, our study offers evidence that downregulated EZH2 or elevated miR-139-5p inhibits ox-LDLinduced HASMCs apoptosis, plaque formation and inflammatory response in AS mice, which may be related to down-regulated STAT1.…”

Transcriptomic Analyses Revealed Systemic Alterations in Gene Expression in Circulation and Tumor Microenvironment of Colorectal Cancer Patients

“…Among these, AREG, is associated with various types of cancers and inflammatory conditions [61]. Proto-oncogene c-MET, VEGFA, CXCL3 and MMP9, which appear to play roles in CRC biology and immune function [62][63][64] are also up regulated.…”

Triticum vulgare Extract Modulates Protein-Kinase B and Matrix Metalloproteinases 9 Protein Expression in BV-2 Cells: Bioactivity on Inflammatory Pathway Associated with Molecular Mechanism Wound Healing

“…The final visualization of the heat map was obtained based on the intensity of the fold-charge evaluated (Figure 3). The articles that we have been using for this part of our work covered the following topics: brain injury [25,26], inflammatory mechanism [27][28][29][30][31][32], and cancer [33][34][35][36][37]. The specifications of papers included in these analyses are reported in Table 1. 2.10.…”