Dataset Information

Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis.

ABSTRACT:

Background

Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. However, the association between TUG1 and Rg3 remains elusive.

Methods

A sepsis mouse model was established by caecal ligation and puncture (CLP), and liver injury was induced by haematoxylin-eosin (H&E) staining. Lipopolysaccharide (LPS) was used to induce hepatocyte damage. The expression levels of TUG1, microRNA (miR)-200a-3p, and silencing information regulator 1 (SIRT1) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) assays. Cell viability was monitored using the Cell Counting Kit-8 (CCK-8) assay. MitoSOX Red staining and CBIC2 (JC-1) dye were employed to detect mitochondrial reactive oxygen species (ROS) and mitochondrial transmembrane potential (MTP) levels, respectively. The interaction between miR-200a-3p and TUG1 or SIRT1 was confirmed via dual-luciferase reporter or RNA immunoprecipitation (RIP) assay.

Results

Rg3 upregulated TUG1 expression in liver tissues of CLP mice and LPS-induced hepatocytes. Rg3 could activate autophagy to improve mitochondrial dysfunction in LPS-treated hepatocytes, which was partially reversed by TUG1 depletion or miR-200a-3p overexpression. Importantly, TUG1 targeted miR-200a-3p to activate the SIRT1/AMP-activated protein kinase (AMPK) pathway in LPS-treated hepatocytes. Moreover, gain of TUG1 ameliorated mitochondrial dysfunction in LPS-treated hepatocytes by sequestering miR-200a-3p.

Conclusion

Our study revealed that Rg3 increased TUG1 expression and reduced miR-200a-3p expression to stimulate the SIRT1/AMPK pathway, thereby enhancing autophagy to improve sepsis-induced liver injury and mitochondrial dysfunction.

SUBMITTER: Wu P

PROVIDER: S-EPMC8686388 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis.

Wu Pan P Yu Xiao X Peng Yue Y Wang Qian-Lu QL Deng Long-Tian LT Xing Wei W Xing Wei W

Journal of inflammation (London, England) 20211220 1

<h4>Background</h4>Studies have shown that ginsenoside R3 (Rg3) plays a protective role in sepsis-induced organ injuries and mitochondrial dysfunction. Long noncoding RNA (lncRNA) taurine-upregulated gene 1 (TUG1) is regarded as a regulator in sepsis. However, the association between TUG1 and Rg3 remains elusive.<h4>Methods</h4>A sepsis mouse model was established by caecal ligation and puncture (CLP), and liver injury was induced by haematoxylin-eosin (H&E) staining. Lipopolysaccharide (LPS) wa ...[more]

PMID: 34930287

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Project description:Platinum-based cytotoxic chemotherapy is considered the standard treatment for advanced gastric cancer (GC). However, cisplatin chemoresistance often occurs with the mechanisms being not well clarified, which results in the cancer recurrence and poor survival. Ginsenoside Rg3, isolated from the Chinese Herb Panax Ginseng, is recognized as an anti-cancer agent. Herein, we aimed to reveal whether Ginsenoside Rg3 alleviates cisplatin resistance and sensitizes GC cells to cisplatin-induced apoptosis, and draw out the underlying molecular mechanism in cisplatin-resistant GC cells. The lower expression of miR-429 was found in AGSR-CDDP cells; it was also in association with cisplatin-resistance in GC cells and expression of which was restored following Ginsenoside Rg3 treatment. We also demonstrated that miR-429 made a contribution toward chemosensitivity in GC cells partly through SOX2 regulation. SOX2 was found to contribute to developing platinum resistance and was an authentic target for miR-429 in AGSR-CDDP cells. Importantly, enforced expression of SOX2 with a pcDNA3-SOX2 construct lacking the 3'-UTR miRNA binding site diminished the cytotoxic effects of miR-429 in AGSR-CDDP cells. We demonstrated that Ginsenoside Rg3 enhanced chemosensitivity in AGSR-CDDP GC cells, at least in part, through up-regulating miR-429, thereby targeting SOX2 and modulating downstream PI3K/AKT/mTOR signaling. Ginsenoside Rg3 was also found to regulate apoptosis-related genes via miR-429 in cisplatin-resistant GC cells. Ginsenoside Rg3 treatment significantly suppressed the migration rate of AGSR-CDDP GC cells, while following transfection with anti-miR-429, the anti-migratory effects of Ginsenoside Rg3 was partially abolished. This data suggested that Ginsenoside Rg3 may impede the chemoresistance and migration of GC cells mainly mediated through miR-429. We concluded that miR-429-regulated SOX2 expression was one of the main mechanisms by which Ginsenoside Rg3 dramatically promoted its anticancer effects on cisplatin-resistant GC cells. We also underscored a supporting model in which miR-429 adjusted PI3K/AKT/mTOR signaling by regulating SOX2 in cisplatin-resistant GC cells.

Dataset Information

Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis.

Background

Methods

Results

Conclusion

Publications

Ginsenoside Rg3 alleviates septic liver injury by regulating the lncRNA TUG1/miR-200c-3p/SIRT1 axis.

Similar Datasets

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