Liver proliferation: The GUCD1/NEDD4–1 connection

Calvisi, Diego F.

doi:10.4161/cc.29535

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Next, we explored the underlying mechanisms involved in the regulation of HCC by miR-370. GUCD1 is an important tumor-related modulator, and a previous study suggested that GUCD1 has an important influence on tumor development, including HCC 31. Here, the current study indicates that GUCD1 expression is inversely associated with miR-370 expression in HCC.…”

Section: Discussionsupporting

confidence: 64%

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1

2019

Yonsei Med J

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Purpose Hepatocellular carcinoma (HCC) is a highly aggressive malignant tumor, the prognosis of which remains poor. Recently, microRNAs have been reported to play crucial functions in multiple tumors, including HCC. However, the molecular mechanisms of miR-370 in HCC still remain largely unknown. The present study focused on the effects of miR-370 on HCC migration, invasion, and epithelial-mesenchymal transition (EMT). Materials and Methods We investigated the key roles and possible regulatory mechanism of miR-370 in regulating HCC metastasis with functional assays, such as transwell assay. Quantitative real-time PCR (qRT-PCR) was used to detect miR-370 and guanylylcyclase domain containing 1 (GUCD1) expression in HCC tissues and cells. Subsequently, we performed transwell assays to determine the functions of miR-370 in HCC cell invasion and migration. Western blot was used to determine protein expressions of relevant genes. Luciferase reporter assays were conducted to confirm the target gene of miR-370. Results qRT-PCR analysis demonstrated that miR-370 was dramatically downregulated in HCC. Moreover, downregulated miR-370 was found to be associated with poor survival and adverse clinicopathologic characteristics of HCC patients. Transwell assays revealed that miR-370 overexpression dramatically suppressed HCC invasion and migration. Meanwhile, miR-370 restoration prominently inhibited EMT progression in HCC cells. Luciferase reporter assays confirmed GUCD1 as a downstream target gene of miR-370. GUCD1 expression in HCC tissues was prominently increased and inversely correlated with miR-370 expression. Furthermore, GUCD1 was verified as mediating the suppressive influence of miR-370 on cell metastasis and EMT in HCC. Conclusion Taken together, our study confirmed that miR-370 suppressed HCC cell metastasis and EMT via regulating GUCD1 . Accordingly, the miR-370/GUCD1 axis may potentially acts as attractive therapeutic targets and novel biomarkers for HCC treatment.

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Section: Discussionsupporting

confidence: 64%

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1

2019

Yonsei Med J

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“…Guanylate cyclases (Guanylate_cyc_2, PF09778) catalyze the conversion of GTP to cGMP, for example, Arabidopsis GC1 protein ( 72 ). Human ortholog, GUCD1 (LLN4), interacts with NEDD4-1 affecting tumor suppressors ( 73 ) and lacks the domain providing the cyclase function described for GC1. Hence, the biological function of this papain-like domain within this family might not be connected to cyclase explicitly.…”

Section: Resultsmentioning

confidence: 99%

Identification and classification of papain-like cysteine proteinases

Ozhelvaci

Steczkiewicz

2023

Journal of Biological Chemistry

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“…The KO murine models provide incontrovertible proof of the relevance of these molecules for a successful liver regeneration. In addition to the IL-6/JAK/STAT3 pathway, there are several effectors that enhance mitogenic signalling in hepatocyte proliferation, such as guanylyl cyclase domain containing 1 (GUCD1), which is strongly up-regulated in the first hours after PH [ 93 , 94 ]. The reduction in GUCD1 levels is guaranteed by NEDD4-mediated neddylation, that promotes proteasomal degradation [ 82 ].…”

Section: Molecular Mechanisms Of Liver Regenerationmentioning

confidence: 99%

Liver Regeneration and Immunity: A Tale to Tell

Di-Iacovo

Pieroni

Piobbico

et al. 2023

IJMS

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The physiological importance of the liver is demonstrated by its unique and essential ability to regenerate following extensive injuries affecting its function. By regenerating, the liver reacts to hepatic damage and thus enables homeostasis to be restored. The aim of this review is to add new findings that integrate the regenerative pathway to the current knowledge. An optimal regeneration is achieved through the integration of two main pathways: IL-6/JAK/STAT3, which promotes hepatocyte proliferation, and PI3K/PDK1/Akt, which in turn enhances cell growth. Proliferation and cell growth are events that must be balanced during the three phases of the regenerative process: initiation, proliferation and termination. Achieving the correct liver/body weight ratio is ensured by several pathways as extracellular matrix signalling, apoptosis through caspase-3 activation, and molecules including transforming growth factor-beta, and cyclic adenosine monophosphate. The actors involved in the regenerative process are numerous and many of them are also pivotal players in both the immune and non-immune inflammatory process, that is observed in the early stages of hepatic regeneration. Balance of Th17/Treg is important in liver inflammatory process outcomes. Knowledge of liver regeneration will allow a more detailed characterisation of the molecular mechanisms that are crucial in the interplay between proliferation and inflammation.

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Liver proliferation: The GUCD1/NEDD4–1 connection

Cited by 6 publications

References 7 publications

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1

MicroRNA-370 Regulates Cellepithelial-Mesenchymal Transition, Migration, Invasion, and Prognosis of Hepatocellular Carcinoma by Targeting GUCD1

Identification and classification of papain-like cysteine proteinases

Liver Regeneration and Immunity: A Tale to Tell

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