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Updated: Dec 27, 2025
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Circular RNA TUBD1 Acts as the miR-146a-5p Sponge to Affect the Viability and Pro-Inflammatory Cytokine Production of
Hao Niu1, Li Zhang1, Yu-Han Chen2
1Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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.
Insights
Circular RNA circTUBD1 is upregulated in radiation-induced liver disease (RILD) models. Silencing circTUBD1 impacts cell viability and inflammation, suggesting it
Area of Science:
- Molecular Biology
- Hepatology
- Immunology
Background:
- The role of circular RNAs (circRNAs) in radiation-induced liver disease (RILD) is largely unknown.
- Hepatic stellate cells (HSCs) are crucial in liver injury and inflammation.
Purpose of the Study:
- To investigate the expression and function of a novel circRNA, circTUBD1, in human hepatic stellate cells (LX-2) under radiation and lipopolysaccharide (LPS) stimulation.
- To elucidate the molecular mechanism of circTUBD1 in regulating cellular responses to injury.
Main Methods:
- Quantitative analysis of circTUBD1 expression in LX-2 cells.
- RNA interference (siRNA) to silence circTUBD1.
- Assessment of cell proliferation and apoptosis.
- Measurement of pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α).
- Analysis of the circTUBD1/miR-146a-5p interaction and downstream signaling pathways (TLR4, IRAK1, TRAF6, pNF-κB).
Main Results:
- CircTUBD1 expression was significantly increased in irradiated and LPS-stimulated LX-2 cells.
- Silencing circTUBD1 reduced LX-2 cell proliferation, induced apoptosis, and decreased pro-inflammatory cytokine production.
- CircTUBD1 functions as a molecular sponge for miR-146a-5p, modulating the TLR4 signaling pathway.
Conclusions:
- CircTUBD1 plays a critical role in regulating the viability and inflammatory response of hepatic stellate cells.
- The circTUBD1/miR-146a-5p/TLR4 pathway is implicated in the pathogenesis of RILD.
- CircTUBD1 represents a potential therapeutic target for RILD.
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