Gan-Jiang-Ling-Zhu decoction alleviates hepatic steatosis in rats by the miR-138-5p/CPT1B axis

Dang, Yanqi; Xu, Jing-Juan; Zhu, Meizhen; Zhou, Wenjun; Zhang, Li; Ji, Guang

doi:10.1016/j.biopha.2020.110127

Cited by 23 publications

(16 citation statements)

References 30 publications

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“…To perform this assay, 293 T cells were seeded on 24-well plates and transfected using FuGene HD transfection reagent (E2311, Promega) per the protocol used in a previous study [ 28 ]. In brief, 293 T cells were transfected with CRB3 wild type (CRB3-WT; Genomeditech) or CRB3 variant (CRB3-Mut; Genomeditech) plasmid with or without METTL3 knockdown for 6 h. Luciferase activity was detected using the dual-luciferase reporter system (E1910, Promega).…”

Section: Methodsmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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Background Colorectal carcinoma (CRC) is the third most common cancer and second most common cause of cancer-related deaths worldwide. Ribonucleic acid (RNA) N6-methyladnosine (m6A) and methyltransferase-like 3 (METTL3) play key roles in cancer progression. However, the roles of m6A and METTL3 in CRC progression require further clarification. Methods Adenoma and CRC samples were examined to detect m6A and METTL3 levels, and tissue microarrays were performed to evaluate the association of m6A and METTL3 levels with the survival of patients with CRC. The biological functions of METTL3 were investigated through cell counting kit-8, wound healing, and transwell assays. M6A epitranscriptomic microarray, methylated RNA immunoprecipitation-qPCR, RNA stability, luciferase reporter, and RNA immunoprecipitation assays were performed to explore the mechanism of METTL3 in CRC progression. Results M6A and METTL3 levels were substantially elevated in CRC tissues, and patients with CRC with a high m6A or METTL3 levels exhibited shorter overall survival. METTL3 knockdown substantially inhibited the proliferation, migration, and invasion of CRC cells. An m6A epitranscriptomic microarray revealed that the cell polarity regulator Crumbs3 (CRB3) was the downstream target of METTL3. METTL3 knockdown substantially reduced the m6A level of CRB3, and inhibited the degradation of CRB3 mRNA to increase CRB3 expression. Luciferase reporter assays also showed that the transcriptional level of wild-type CRB3 significantly increased after METTL3 knockdown but not its level of variation. Knockdown of YT521-B homology domain–containing family protein 2 (YTHDF2) substantially increased CRB3 expression. RNA immunoprecipitation assays also verified the direct interaction between the YTHDF2 and CRB3 mRNA, and this direct interaction was impaired after METTL3 inhibition. In addition, CRB3 knockdown significantly promoted the proliferation, migration, and invasion of CRC cells. Mechanistically, METTL3 knockdown activated the Hippo pathway and reduced nuclear localization of Yes1-associated transcriptional regulator, and the effects were reversed by CRB3 knockdown. Conclusions M6A and METTL3 levels were substantially elevated in CRC tissues relative to normal tissues. Patients with CRC with high m6A or METTL3 levels exhibited shorter overall survival, and METTL3 promoted CRC progression. Mechanistically, METTL3 regulated the progression of CRC by regulating the m6A–CRB3–Hippo pathway.

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Section: Methodsmentioning

confidence: 99%

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Pan

Liu

Xiao

et al. 2022

J Exp Clin Cancer Res

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“…It has been reported that miR‐138‐5p is involved in the progression of multiple diseases by regulating lipogenesis (Liu et al, 2020), inhibiting oxidative stress (Wang, Sun, Yao, Tang, & Wu, 2019), and inducing inflammatory response (Hu et al, 2020). In the previous study (Dang et al, 2020), the author found that GJLZ is an effective formula for NAFLD management, and its possible mechanism of action involves the regulation of CPT1B expression via rno‐miR‐138‐5p in rats. In our study, ISL significantly promoted lipid metabolism and inhibited inflammatory response in human liver LO2 cells, and it was further verified in C57BL6/J mice.…”

Section: Discussionmentioning

confidence: 98%

“…The It has been reported that miR-138-5p is involved in the progression of multiple diseases by regulating lipogenesis (Liu et al, 2020), inhibiting oxidative stress (Wang, Sun, Yao, Tang, & Wu, 2019), and inducing inflammatory response (Hu et al, 2020). In the previous study (Dang et al, 2020), the author found that GJLZ is an effective…”

Section: Isl Alleviated Nafld In Vivomentioning

confidence: 95%

Activation of PGC‐1α via isoliquiritigenin‐induced downregulation of miR‐138‐5p alleviates nonalcoholic fatty liver disease

Wang

Kong

et al. 2022

Phytotherapy Research

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Nonalcoholic fatty liver disease (NAFLD), a metabolic disease, has received wide attention worldwide. However, there is no approved effective drug for NAFLD treatment. In the study, H&E and Oil Red O staining were employed to detect liver histopathological changes and the accumulation of lipid droplets. Quantitative real-time PCR, Western blot, bioinformatics, luciferase assay, immunofluorescence staining, reactive oxygen species (ROS), and siRNA were used to further elucidate the mechanism of isoliquiritigenin (ISL) against NAFLD. The results showed that ISL significantly reduced the liver-to-body weight ratios and biochemical index. And the staining results showed that ISL remarkedly ameliorated liver histopathological changes of NAFLD. Furthermore, ISL significantly increased the levels of PPARα, CPT1α, and ACADS, which were involved in lipid metabolism, and inhibited the ROS, TNF-α, IL-1β, and IL-6 expression by activating PGC-1α. Bioinformatics and luciferase assay analysis confirmed that miR-138-5p might bind to PGC-1α mRNA in NAFLD. Importantly, the expression of miR-138-5p was increased in the NAFLD, which was significantly decreased by ISL. In addition, the miR-138-5p inhibitor also promoted lipid metabolism and inhibited inflammatory response in NAFLD via PGC-1α activation.The above results demonstrate that ISL alleviates NAFLD through modulating miR-138-5p/PGC-1α-mediated lipid metabolism and inflammatory reaction in vivo and in vitro.

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“…The fixed liver sections were dehydrated, embedded, and sectioned into 4 μ m sections for staining with hematoxylin and eosin (H&E). The frozen liver sections were embedded and sectioned into 10 μ m thick sections using a frozen microtome (Leica, Germany) for staining with Oil Red O, according to previous studies [ 25 , 26 ].…”

Section: Methodsmentioning

confidence: 99%

Quantitative Profiling of Oxylipin Reveals the Mechanism of Pien-Tze-Huang on Alcoholic Liver Disease

Zhu

Zhou

Yang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Alcoholic liver disease (ALD) is a liver disease caused by long-term alcohol consumption. ROS-mediated oxidative stress is the leading cause of ALD. Pien-Tze-Huang (PZH), a traditional formula, is famous in China. This study was designed to evaluate the effects and explore the potential mechanisms of PZH in ALD. Forty mice were randomly divided into five groups: control group (normal diet + vehicle), model group (ethanol diet + vehicle), PZH-L group (ethanol diet + PZH (0.125 g/kg)), PZH-M group (ethanol diet + PZH (0.25 g/kg)), and PZH-H group (ethanol diet + PZH (0.5 g/kg)). The mice were sacrificed, and their liver and blood samples were preserved. Liver steatosis, triglyceride (TG), total cholesterol, serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were assayed. Malondialdehyde (MDA), glutathione peroxidase (GSH-PX), and total superoxide dismutase were identified using commercial kits. Oxylipins were profiled, and the data were analyzed. The AMPK/ACC/CPT1A pathway was identified using real-time polymerase chain reaction and western blotting. The PZH-H intervention significantly alleviated hepatic steatosis and injury and reduced the levels of liver TG and serum ALT and AST. In addition, MDA levels were markedly reduced, and GSH-PX activity significantly increased after PZH-H intervention. Finally, PZH-H increased the levels of 17-HETE, 15-HEPE, 9-HOTrE, 13-HOTrE, and 5,6-dihydroxy-8Z,11Z,14Z,17Z-eicosatetraenoic acid, and reduced PGE2 levels. PZH-H intervention also promoted the phosphorylation of AMPK and ACC, and the expression of CPT1A. In conclusion, PZH reduced oxidative stress and alleviated hepatic steatosis and injury. The mechanism was correlated with the oxylipin metabolites/AMPK/ACC/CPT1A axis.

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Gan-Jiang-Ling-Zhu decoction alleviates hepatic steatosis in rats by the miR-138-5p/CPT1B axis

Cited by 23 publications

References 30 publications

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

METTL3 promotes colorectal carcinoma progression by regulating the m6A–CRB3–Hippo axis

Activation of PGC‐1α via isoliquiritigenin‐induced downregulation of miR‐138‐5p alleviates nonalcoholic fatty liver disease

Quantitative Profiling of Oxylipin Reveals the Mechanism of Pien-Tze-Huang on Alcoholic Liver Disease

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