Downregulation of miR‑141 deactivates hepatic stellate�cells by targeting the PTEN/AKT/mTOR pathway

Liang, Haijun; Wang, Xinwei; Si, Changyun; Duan, Yuxiu; Chen, Baoxin; Liang, Haixia; Yang, Daokun

doi:10.3892/ijmm.2020.4578

Cited by 11 publications

(12 citation statements)

References 46 publications

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“…showed that miR-141 attenuated autophagy-mediated hepatitis B virus inhibition (Yang et al., 2017 ). Moreover, Liang’s team demonstrated that miR-141 was elevated in activated HSCs, and promoted HSC activation with the increased expression levels of pro-fibrotic markers by activating AKT/mTOR pathway through repressing PTEN (Liang et al., 2020 ). In the present study, we also confirmed that inhibition of miR-141-3p suppressed HSC activation by regulating the actions mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis

Wei

Zeng

et al. 2022

Drug Delivery

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Liver fibrosis is a common pathologic stage of the development of liver failure. It has showed that exosomes loaded with therapeutic circRNAs can be manufactured in bulk by exosome secreted cells in vitro , thus enabling personalized treatment. This study aimed to investigate the role of exosome-based delivery of circDIDO1 in liver fibrosis. Levels of genes and proteins were examined by qRT-PCR and Western blot. Cell proliferation, apoptosis, and cell cycle were analyzed by using cell counting kit-8 (CCK-8) assay, EdU assay, and flow cytometry, respectively. The binding between circDIDO1 and miR-141-3p was confirmed by dual-luciferase reporter, RNA pull-down and RIP assays. Exosomes were isolated by ultracentrifugation, and qualified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and Western blot. CircDIDO1 overexpression or miR-141-3p inhibition suppressed the proliferation, reduced pro-fibrotic markers, and induced apoptosis as well as cell cycle arrest in hepatic stellate cells (HSCs) by blocking PTEN/AKT pathway. Mechanistically, circDIDO1 acted as an endogenous sponge for miR-141-3p, further rescue experiments showed that circDIDO1 suppressed HSC activation by targeting miR-141-3p. Extracellular circDIDO1 could be incorporated into exosomes isolated from mesenchymal stem cells (MSCs), and transmitted to HSCs to restrain HSC activation. Clinically, low levels of serum circDIDO1 in exosome were correlated with liver failure, and serum exosomal circDIDO1 had a well diagnostic value for liver fibrosis in liver failure patients. Transfer of circDIDO1 mediated by MSC-isolated exosomes suppressed HSC activation through the miR-141-3p/PTEN/AKT pathway, gaining a new insight into the prevention of liver fibrosis in liver failure patients.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis

Wei

Zeng

et al. 2022

Drug Delivery

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“…25,26 In hepatic stellate cells, TGF-β1 regulated PTEN/Akt/mTOR pathway through miR-141. 27 These recent studies indicate that TGF-β1 regulates PTEN expression via miRNAs rather than directly bind to PTEN, which may be a direction for clarifying the detail mechanism of this study.…”

mentioning

confidence: 72%

<p>Xanthohumol Inhibits TGF-β1-Induced Cardiac Fibroblasts Activation via Mediating PTEN/Akt/mTOR Signaling Pathway</p>

Jiang¹,

Xie²,

Sun³

et al. 2020

DDDT

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“…Several recent studies have focused on the role of regulatory non-coding RNAs, such as miRNAs and long intergenic non-coding RNAs (lincRNAs) in the activation of HSCs by affecting PTEN. MiR-21 (Hao et al, 2018), -140-3p (Wu et al, 2019), -141 (Liang et al, 2020), and -1273g-3p (Niu et al, 2016) have been shown to be negative regulators of PTEN, which lead to HSCs activation, cell apoptosis inhibition, and fibrosis formation through regulating the PI3K/AKT or AKT/mTOR pathway. Additionally, Dicer, an enzyme with endonuclease activity, is involved in cutting precursor miRNAs to produce functional forms.…”

Section: Hepatic Fibrosismentioning

confidence: 99%

“…Niu et al, 2016;Yu Q. et al, 2017;Hao et al, 2018;Wu et al, 2019;Dong et al, 2019Dong et al, , 2020Geng et al, 2020;Liang et al, 2020Bian et al, 2012Yang et al, 2017Yang et al, 2017Yu F. et al, 2017 Yu F. et almiRNAs, microRNAs; lincRNA, long non-coding RNAs; IBD, inflammatory bowel disease; AP, acute pancreatitis; NAFLD, non-alcoholic fatty liver disease; HSCs, hepatic stellate cells; HOTAIR, homeobox transcript antisense RNA; PSCs, Pancreatic stellate cells; ROS, Reactive oxygen species.…”

mentioning

confidence: 99%

Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

Zhang

Hao

et al. 2021

Front. Physiol.

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The Phosphatase and tensin homolog (PTEN) gene is one of the most important tumor suppressor genes, which acts through its unique protein phosphatase and lipid phosphatase activity. PTEN protein is widely distributed and exhibits complex biological functions and regulatory modes. It is involved in the regulation of cell morphology, proliferation, differentiation, adhesion, and migration through a variety of signaling pathways. The role of PTEN in malignant tumors of the digestive system is well documented. Recent studies have indicated that PTEN may be closely related to many other benign processes in digestive organs. Emerging evidence suggests that PTEN is a potential therapeutic target in the context of several non-neoplastic diseases of the digestive tract. The recent discovery of PTEN isoforms is expected to help unravel more biological effects of PTEN in non-neoplastic digestive diseases.

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Downregulation of miR‑141 deactivates hepatic stellate�cells by targeting the PTEN/AKT/mTOR pathway

Cited by 11 publications

References 46 publications

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis

Mesenchymal stem cell-originated exosomal circDIDO1 suppresses hepatic stellate cell activation by miR-141-3p/PTEN/AKT pathway in human liver fibrosis

<p>Xanthohumol Inhibits TGF-β1-Induced Cardiac Fibroblasts Activation via Mediating PTEN/Akt/mTOR Signaling Pathway</p>

Phosphatase and Tensin Homolog in Non-neoplastic Digestive Disease: More Than Just Tumor Suppressor

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