Inhibition of miR‐103a‐3p suppresses lipopolysaccharide‐induced sepsis and liver injury by regulating FBXW7 expression

Abstract

Inflammation, apoptosis, and oxidative stress are involved in septic liver dysfunction. Herein, the role of miR‐103a‐3p/FBXW7 axis in lipopolysaccharides (LPS)‐induced septic liver injury was investigated in mice. Hematoxylin‐eosin staining was used to evaluate LPS‐induced liver injury. Quantitative real‐time polymerase chain reaction was performed to determine the expression of microRNA (miR) and messenger RNA, and western blot analysis was conducted to examine the protein levels. Dual‐luciferase reporter assay was used to confirm the binding between miR‐103a‐3p and FBXW7. Both annexin V‐fluoresceine isothiocyanate/propidium iodide staining and caspase‐3 activity were employed to determine cell apoptosis. First, miR‐103a‐3p was upregulated in the septic serum of mice and patients with sepsis, and miR‐103a‐3p was elevated in the septic liver of LPS‐induced mice. Then, interfering miR‐103a‐3p significantly decreased apoptosis by suppressing Bax expression and upregulating Bcl‐2 levels in LPS‐induced AML12 and LO2 cells, and septic liver of mice. Furthermore, inhibition of miR‐103a‐3p repressed LPS‐induced inflammation by downregulating the expression of tumor necrosis factor, interleukin 1β, and interleukin 6 in vitro and in vivo. Meanwhile, interfering miR‐103a‐3p obviously attenuated LPS‐induced overactivation of oxidation via promoting expression of antioxidative enzymes, including catalase, superoxide dismutase, and glutathione in vitro and in vivo. Moreover, FBXW7 was a target of miR‐103a‐3p, and overexpression of FBXW7 significantly ameliorated LPS‐induced septic liver injury in mice. Finally, knockdown of FBXW7 markedly reversed anti‐miR‐103a‐3p‐mediated suppression of septic liver injury in mice. In conclusion, interfering miR‐103a‐3p or overexpression of FBXW7 improved LPS‐induced septic liver injury by suppressing apoptosis, inflammation, and oxidative reaction.

Expression of MicroRNAs in Sepsis-Related Organ Dysfunction: A Systematic Review

“…Zhou and Xia reported high levels of miR-103a-3p in the liver and serum of LPS septic mice and also in human patients. In vitro miR-103a-3p inhibition suppressed LPS-induced inflammation by downregulating the expression of TNF, IL-1β and IL-6 in vitro and in vivo [ 232 ].…”

Analysis of the Resistance of Small Peptides from Periplaneta americana to Hydrogen Peroxide-induced Apoptosis in KGN Cells based on High-throughput miRNA Sequencing

“…However, miR-103a-3p and miR-214 play an important role when SPPA inhibits oxidative ovarian damage. Zhou et al had reported that interfering with miR-103a-3p is able to inhibit LPS-induced hepatocyte apoptosis, in ammation and oxidation reactions [20]. Cheng et al found that upregulation of miR-103a-3p promoted chondrocyte proliferation of human osteoarthritis (OA) and inhibited cell apoptosis and in ammatory responses [21].…”

Silencing lncRNA TUG1 Alleviates LPS-Induced Mouse Hepatocyte Inflammation by Targeting miR-140/TNF

“…However, the knockdown of TUG1 reversed the damage of LPS. Besides oxidative stress, apoptosis is also accompanied by LPS-induced inflammation ( Chen et al, 2017 ; Lv et al, 2020 ; Zhou and Xia, 2020 ). We further detected apoptotic marker proteins cleaved-caspase 3, Bax, and Bcl 2 in LPS-treated cells, which indicated that silencing TUG1 inhibited LPS-induced cell apoptosis.…”