microRNA‐30a inhibits the liver cell proliferation and promotes cell apoptosis through the JAK/STAT signaling pathway by targeting SOCS‐1 in rats with sepsis

Abstract

Sepsis is a systemic inflammatory response that may be induced by trauma, infection, surgery, and burns. With the aim of discovering novel treatment targets for sepsis, this current study was conducted to investigate the effect and potential mechanism by which microRNA‐30a (miR‐30a) controls sepsis‐induced liver cell proliferation and apoptosis. Rat models of sepsis were established by applying the cecal ligation and puncture (CLP) method to simulate sepsis models. The binding site between miR‐30a and suppressor of cytokine signaling protein 1 (SOCS‐1) was determined by dual luciferase reporter gene assay. The gain‐of‐and‐loss‐of‐function experiments were applied to analyze the effects of miR‐30a and SOCS‐1 on liver cell proliferation and apoptosis of the established sepsis rat models. The expression of miR‐30a, SOCS‐1, Janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), Bcl‐2 associated X protein (Bax), B cell lymphoma‐2 (Bcl‐2), toll‐like receptor 4 (TLR4), and high‐mobility group box 1 (HMGB1), and the extent of JAK2 and STAT3 phosphorylation were all determined. Sepsis led to an elevation of miR‐30a and also a decline of SOCS‐1 in the liver cells. SOCS‐1 was negatively regulated by miR‐30a. Upregulated miR‐30a and downregulated SOCS‐1 increased the expression of JAK2, STAT3, Bax, TLR4, and HMGB1 as well as the extent of JAK2 and STAT3 phosphorylation whereas impeding the expression of SOCS‐1 and Bcl‐2. More important, either miR‐30a elevation or SOCS‐1 silencing suppressed liver cell proliferation and also promoted apoptosis. On the contrary, the inhibition of miR‐30a exhibited the opposite effects. Altogether, we come to the conclusion that miR‐30a inhibited the liver cell proliferation and promoted cell apoptosis by targeting and negatively regulating SOCS‐1 via the JAK/STAT signaling pathway in rats with sepsis.

JAK/STAT signaling pathway-mediated microRNA-181b promoted blood-brain barrier impairment by targeting sphingosine-1-phosphate receptor 1 in septic rats

“…Monitoring blood D-lactate levels can reflect intestinal permeability changes and the extent of damage (34). Studies have also revealed a higher content of TNF-α, IL-6, and IL-8 in sepsis serum than in serum from sham-operated rats (14,35), which was consistent with the findings of the present study. In addition to serum, the levels of TNF-α, IL-6, and IL-8 have also been reported to be increased in the intestines (36).…”

“…JAK/STAT signaling pathway has been shown related to the release of various cytokines and inflammatory mediators and involved in the regulation of immune response in sepsis (7,8). Some other miRNAs, as miRNA-30a and miR-155 were also reported regulated sepsis-induced liver injury through regulating JAK/STAT signaling pathway (14,15). In the present study, we confirmed the relationship between miR-181b, JAK/STAT signaling pathway on influencing permeability of BBB.…”

“…JAK/STAT signaling pathway has also been shown to regulate the levels of serum factors used in the diagnosis and prognosis of sepsis patients (13). Moreover, miRNA-30a and miR-155 were reported to relieve sepsis-induced liver injury through inactivating JAK/ STAT pathway (14,15). Considering that inflammatory cytokines were released by JAK/STAT signaling pathway and was harmful for BBB, we wondered whether JAK/ STAT signaling pathway regulates the BBB or further influences SAE, and if so, how.…”

The Coronavirus PEDV Evades Type III Interferon Response Through the miR-30c-5p/SOCS1 Axis

“…JEV infection downregulates the expression of miRNA miR-432, which directly targets the suppressor of cytokine signaling protein 5 (SOCS5) and manipulates the JAK-STAT1 signaling cascade (Sharma et al, 2016). The miR-30 family has been reported to target SOCS family members and manipulate the JAK/STAT signaling pathway (Zou et al, 2017;Ma et al, 2018;Yuan et al, 2019). In this study, we showed that PEDV infection suppressed miR-30c-5p expression, which was conversely related to SOCS1 expression during PEDV infection (Figure 4).…”

“…In this study, we showed that PEDV infection suppressed miR-30c-5p expression, which was conversely related to SOCS1 expression during PEDV infection (Figure 4). Just as other members of miR-30, miR-30c-5p specifically targeted the 3 ′ UTR of SOCS1 and inhibited SOCS1 expression (Kobayashi et al, 2012;Ma et al, 2018;Yuan et al, 2019) (Figure 4). However, the mechanism of PEDV decreasing miR-30a-5p remains unclear and deserves further study.…”