Circular RNA TUBD1 Acts as the miR-146a-5p Sponge to Affect the Viability and Pro-Inflammatory Cytokine Production of LX-2 Cells through the TLR4 Pathway
Journal
Radiation Research
Journal Volume
193
Journal Issue
4
Pages
383-393
Date Issued
2020
Author(s)
Abstract
The functions and molecular mechanism of circRNAs in the development of radiation-induced liver disease (RILD) remain largely unknown. The goal of this study was to explore the expression and potential role of a new circular RNA, named circTUBD1, in irradiated and lipopolysaccharide (LPS)-stimulated human hepatic stellate cell (HSC) line LX-2 cells. The expression of circTUBD1 was significantly upregulated in irradiated and LPS-stimulated LX-2 cells compared to non-treated LX-2 cells. To explore the functions of circTUBD1, small interfering RNAs targeting circTUBD1 were designed. Silencing circTUBD1 inhibited proliferation, promoted apoptosis of LX-2 cells, and significantly decreased the expression level of pro-inflammatory cytokines, including IL-1β, IL-6 and TNF-α in irradiated and LPS-stimulated LX-2 cells. Mechanistic analysis suggested that circTUBD1 acted as the miR-146a-5p sponge to affect pro-inflammatory cytokine production through regulating expression of Toll-like receptor 4 (TLR4), interleukin receptor-associated kinase 1 (IRAK1), tumor necrosis factor receptor-associated factor-6 (TRAF6), and phosphorylation of nuclear factor-kappa B (pNF-κB) in irradiated and LPS-stimulated LX-2 cells. To our knowledge, this is the first study to show that circTUBD1 acts as a miR-146a-5p sponge to affect the viability and pro-inflammatory cytokine production of LX-2 cells through the TLR4 pathway, suggesting that circTUBD1 is a potential target for RILD therapy. ? 2020 by Radiation Research Society. All rights of reproduction in any form reserved.
SDGs
Other Subjects
circular ribonucleic acid; circular ribonucleic acid TUBD1; immunoglobulin enhancer binding protein; interleukin 1; interleukin 1beta; interleukin 6; interleukin receptor associated kinase 1; microRNA; microRNA 146a 5p; phosphotransferase; small interfering RNA; toll like receptor 4; tumor necrosis factor; tumor necrosis factor receptor associated factor 6; unclassified drug; cytokine; microRNA; MIRN146 microRNA, human; TLR4 protein, human; toll like receptor 4; TUBD1 protein, human; tubulin; apoptosis; Article; cell proliferation; cytokine production; gene expression; hepatic stellate cell; human; human cell; priority journal; biosynthesis; cell survival; genetics; liver; liver disease; metabolism; pathology; radiation induced malformation; radiation response; signal transduction; Abnormalities, Radiation-Induced; Cell Survival; Cytokines; Hepatic Stellate Cells; Humans; Liver; Liver Diseases; MicroRNAs; RNA, Circular; Signal Transduction; Toll-Like Receptor 4; Tubulin
Publisher
Radiation Research Society
Type
journal article