Impact of miR‐140 Deficiency on Non‐Alcoholic Fatty Liver Disease

Wolfson, Benjamin; Lo, Pang-Kuo; Yao, Yuan; Li, Linhao; Wang, Hongbing; Zhou, Qun

doi:10.1002/mnfr.201800189

Cited by 12 publications

(7 citation statements)

References 54 publications

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“…miR-140-3p has a pro-fibrosis effect. It has been demonstrated that miR-140-3p has a pro-fibrotic effect in the mammary gland14 and is deeply involved in liver disorders,131516 including hepatic impact injury, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Progressive liver fibrosis is observed in the late stages of various chronic liver diseases, and miR-140 has been predicted to be upregulated in rat HSCs during activation 12.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, increasing expression thereof during the development of fibrosis of the liver and progressive liver fibrosis have been posited in the late stages of various chronic liver diseases. Research has demonstrated that miR-140-3p has a pro-fibrotic effect in the mammary glands14 and is deeply involved in liver disorders,121516 including hepatic impact injury, non-alcoholic fatty liver disease, and hepatocellular carcinoma. Thus, we planned to investigate the role of miR-140-3p in HSC activation and its molecular signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

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miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Huang

et al. 2019

Yonsei Med J

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Purpose Liver fibrosis is a major cause of morbidity and mortality and the outcome of various chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrosis. Studies have confirmed that miR-140-3p plays a potential regulatory effect on HSC activation. However, whether miR-140-3p mediates the liver fibrosis remains unknown. Materials and Methods Expression of miR-140-3p was detected by real-time quantitative PCR (qPCR). Cell proliferation was measured by MTT, while cell apoptosis rate was determined via flow cytometry. Western blot assay was used to detect the expression of cleaved PARP. The fibrogenic effect was evaluated by expression of α-smooth muscle actin and desmin. Functional experiments were performed in transforming growth factor β1 (TGF-β1)-induced HSC-T6 cells with transfection of anti-miR-140-3p and/or siPTEN. Target binding between miR-140-3p and PTEN was predicted by the TargetScan database and identified using luciferase reporter assay and RNA immunoprecipitation. Results TGF-β1 induced the activation of HSC-T6 cells, and miR-140-3p expression varied according to HSC-T6 cell activation status. Knockdown of miR-140-3p reduced cell proliferation and the expressions of α-SMA and desmin, as well as increased apoptosis, in TGF-β1-induced HSC-T6 cells, which could be blocked by PTEN silencing. Additionally, inactivation of the AKT/mTOR signaling pathway stimulated by miR-140-3p knockdown was abolished when silencing PTEN expression. PTEN was negatively regulated by miR-140-3p via direct binding in HSC-T6 cells. Conclusion miR-140-3p is an important mediator in HSC-T6 cell activation, and miR-140-3p knockdown suppresses cell proliferation and fibrogenesis in TGF-β1-induced HSC-T6 cells, indicating that miR-140-3p may be a potential novel molecular target for liver fibrosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Huang

et al. 2019

Yonsei Med J

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“…miRNAs have crucial roles in many cellular processes, as well as in varieties of diseases, including cancers and metabolism-related disorders [ 25 – 28 ]. A great number of dysregulated miRNAs have been reported in NAFLD, such as miR-21, miR-140 [ 16 , 29 ]. miR-206 has been shown to play key roles in development, cell proliferation, and differentiation [ 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1/AMPK signaling through targeting miR-206

Chen

Tan

et al. 2021

Cell Death Dis

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Nonalcoholic fatty liver disease (NAFLD) is one of the most prevalent chronic liver disorders that is featured by the extensive deposition of fat in the hepatocytes. Current treatments are very limited due to its unclear pathogenesis. Here, we investigated the function of circ_0057558 and miR-206 in NAFLD. High-fat diet (HFD) feeding mouse was used as an in vivo NAFLD model and long-chain-free fatty acid (FFA)-treated liver cells were used as an in vitro NAFLD model. qRT-PCR was used to measure levels of miR-206, ROCK1 mRNA, and circ_0057558, while Western blotting was employed to determine protein levels of ROCK1, p-AMPK, AMPK, and lipogenesis-related proteins. Immunohistochemistry were performed to examine ROCK1 level. Oil-Red O staining was used to assess the lipid deposition in cells. ELISA was performed to examine secreted triglyceride (TG) level. Dual-luciferase assay was used to validate interactions of miR-206/ROCK1 and circ_0057558/miR-206. RNA immunoprecipitation was employed to confirm the binding of circ_0057558 with miR-206. Circ_0057558 was elevated while miR-206 was reduced in both in vivo and in vitro NAFLD models. miR-206 directly bound with ROCK1 3’-UTR and suppressed lipogenesis and TG secretion through targeting ROCK1/AMPK signaling. Circ_0057558 directly interacted with miR-206 to disinhibit ROCK1/AMPK signaling. Knockdown of circ_0057558 or overexpression of miR-206 inhibited lipogenesis, TG secretion and expression of lipogenesis-related proteins. ROCK1 knockdown reversed the effects of circ_0057558 overexpression. Injection of miR-206 mimics significantly ameliorated NAFLD progression in vivo. Circ_0057558 acts as a miR-206 sponge to de-repress the ROCK1/AMPK signaling and facilitates lipogenesis and TG secretion, which greatly contributes to NAFLD development and progression.

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“…Finally, these miRNAs have been demonstrated to be associated with pathological outcomes in a number of other hepatocyte models including those modeling HCC. ( 10,37‐47 )…”

Section: Discussionmentioning

confidence: 99%

Serum MicroRNA Signatures in Recovery From Acute and Chronic Liver Injury and Selection for Liver Transplantation

et al. 2020

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We previously demonstrated a distinct hepatic microRNA (miRNA) signature (down-regulation of miRNA-23a, -150, -200b, -503, and -663 and up-regulation of miRNA-20a) is associated with successful regeneration in auxiliary liver transplantation (ALT). This study aimed to evaluate whether the serum expression of this regeneration-linked miRNA signature is associated with clinical outcomes in acute and chronic liver disease. These were represented by patients with acetaminophen-induced acute liver failure (ALF; n = 18) and patients with hepatitis C virus (HCV) undergoing treatment with direct-acting antivirals (n = 56), respectively. Patients were grouped depending on their clinical outcome. Global serum miRNA expression was analyzed using polymerase chain reaction (PCR) arrays and selected miRNA expression using targeted PCR. We demonstrate that specific regeneration-linked miRNAs discriminate outcomes in both clinical scenarios. We further show that miRNA-20a, -23a, -150, -200b, -503, and -663 undergo concordant changes in expression in 3 distinct clinical settings: liver regeneration accompanying successful ALT, clinical recovery after ALF, and clinical recompensation after cure of HCV. This miRNA signature represents a potentially novel biomarker to predict outcome and optimize patient selection for liver transplantation in both acute and chronic liver disease.Liver Transplantation 26 811-822 2020 AASLD. devised and planned the experiments and reviewed and revised the manuscript for submission. Siamak Salehi and Oliver D. Tavabie carried out the microRNA analysis and drafted the manuscript. Suman Verma and William Bernal created the patient cohorts, developed clinical data, and reviewed and revised the manuscript for submission.

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Impact of miR‐140 Deficiency on Non‐Alcoholic Fatty Liver Disease

Cited by 12 publications

References 54 publications

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

miR-140-3p Knockdown Suppresses Cell Proliferation and Fibrogenesis in Hepatic Stellate Cells via PTEN-Mediated AKT/mTOR Signaling

Circ_0057558 promotes nonalcoholic fatty liver disease by regulating ROCK1/AMPK signaling through targeting miR-206

Serum MicroRNA Signatures in Recovery From Acute and Chronic Liver Injury and Selection for Liver Transplantation

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