LINC01419-Mediated Epigenetic Silencing of ZIC1 Promotes Metastasis in Hepatocellular Carcinoma through thePI3K/Akt Signaling Pathway

LINC01419 enhances the methylation of zinc finger of the cerebellum (ZIC1) promoter, inhibits ZIC1 expression, and activates the PI3K/Akt signaling pathway, thereby enhancing the malignant phenotypes of hepatocellular carcinoma cells in vitro as well as tumor formation and metastasis in vivo.
[Laboratory Investigation]
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Interferon Regulatory Factor 1 (IRF-1) Downregulates Checkpoint Kinase 1 (CHK1) through miR-195 to Upregulate Apoptosis and PD-L1 Expression in Hepatocellular Carcinoma (HCC) Cells

IRF-1 induces miR-195 to suppress CHK1 protein expression. Both increased IRF-1 and decreased CHK1 upregulate cellular apoptosis and PD-L1 expression in HCC.
[British Journal of Cancer]
Yan, Y., Zheng, L., Du, Q., Cui, X., Dong, K., Guo, Y., & Geller, D. A. (2021). Interferon regulatory factor 1 (IRF-1) downregulates Checkpoint kinase 1 (CHK1) through miR-195 to upregulate apoptosis and PD-L1 expression in Hepatocellular carcinoma (HCC) cells. British Journal of Cancer, 1–11. https://doi.org/10.1038/s41416-021-01337-6 Cite
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N-n-Butyl Haloperidol Iodide Ameliorates Liver Fibrosis and Hepatic Stellate Cell Activation in Mice

Researchers revealed that c-Jun was bound to the TGF-β receptor II (TGFBR2) promoter, whereas N-n-Butyl haloperidol iodide suppressed the binding of c-Jun to the TGFBR2 promoter to restrain TGF-β signaling and inhibit α-smooth muscle actin and collagen I upregulation.
[Acta Pharmacologica Sinica]
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Direct and Indirect Control of Hepatic Glucose Production by Insulin

The authors make the case that physiologically direct hepatic insulin action dominates acute suppression of glucose production, but that there is also a delayed, second order regulation of this process via extrahepatic effects. They further provide their views regarding the timing, dominance, and physiological relevance of these effects and discuss novel concepts regarding insulin regulation of adipose tissue fatty acid metabolism and central nervous system signaling to the liver, as regulators of insulin’s extrahepatic effects on glucose production.
[Cell Metabolism]
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Terns Announces Initiation of Dosing in Phase I Clinical Trial of TERN-501, its THR-Beta Agonist in Development for the Treatment of NASH

Terns Pharmaceuticals, Inc. announced the initiation of dosing in a Phase I clinical trial evaluating TERN-501, a selective thyroid hormone receptor beta (THR-β) agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β when compared with other THR-β agonists in development.
[Terns Pharmaceuticals, Inc. (Intrado GlobeNewswire LLC.)]
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Tumor Necrosis Factor‐α‐Induced Protein 8‐like 2 Alleviates Nonalcoholic Fatty Liver Disease via Suppressing TAK1 Activation

Tumor necrosis factor‐α‐induced protein 8‐like 2 suppressed nonalcoholic fatty liver disease (NAFLD) advancement by blocking transforming growth factor‐beta‐activated kinase 1‐c‐Jun NH2‐terminal kinase/p38 pathway and was a promising target molecule for NAFLD therapy.
[Hepatology]
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Peptide-Based Scaffolds for the Culture and Maintenance of Primary Human Hepatocytes

Researchers report the use of a nanofibrous hydrogel as a 3D scaffold for the culture and maintenance of functional primary human hepatocytes.
[Scientific Reports]
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Matrix Metalloproteinase-1 Decorated Polymersomes, a Surface-Active Extracellular Matrix Therapeutic, Potentiates Collagen Degradation and Attenuates Early Liver Fibrosis

The therapeutic effects of MMP-1 decorated polymersomes (MMPsomes), compared to matrix metalloproteinase-1 (MMP-1), were evaluated in vivo in carbon-tetrachloride-induced early liver fibrosis mouse model. MMPsomes exhibited favorable physicochemical properties, MMP-1 surface localization and improved therapeutic efficacy in TGFβ-activated human hepatic stellate cells in vitro.
[Journal of Controlled Release]
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5-Methoxytryptophan Alleviates Liver Fibrosis by Modulating FOXO3a/miR-21/ATG5 Signaling Pathway Mediated Autophagy

In vitro, 5-methoxytryptophan (5-MTP) treatment could inhibit TGF-β1-induced elevated levels of collagen I, collagen III, fibronectin and α-smooth muscle actin by stimulating autophagy process. Mechanically, the expression of FOXO3a was enhanced by 5-MTP and then repressed the level of miR-21, eventually leading to a restoration of autophagy-related gene ATG5.
[Cell Cycle]
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IRF2 Regulates Cellular Survival and Lenvatinib-Sensitivity of Hepatocellular Carcinoma (HCC) through Regulating β-Catenin

Silencing Interferon regulatory factorsI (IRF2) downregulated the expression of β-catenin, while overexpressing IRF2 upregulated β-catenin. The expression of β-catenin and IRF2 was positively correlated in HCC tissues. Inhibiting β-catenin with XAV-939 effectively abrogated β-catenin expression caused by lenvatinib treatment.
[Autophagy]
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Hepatic Stellate Cells Promote Intrahepatic Cholangiocarcinoma Progression via NR4A2/osteopontin/Wnt Signaling Axis

By establishing co-culture models of Intrahepatic cholangiocarcinoma (ICC) cells and hepatic stellate cells (HSCs), researchers identified that HSCs triggered the expression of nuclear receptor family 4 subgroup A member 2 (NR4A2), a transcription factor previously reported as a molecular switch between inflammation and cancer, in ICC cells.
[Oncogene]
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