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New insights into the cellular activities of Fndc5/Irisin and its signaling pathways.

ABSTRACT: Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.

SUBMITTER: Rabiee F

PROVIDER: S-EPMC7106581 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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New insights into the cellular activities of Fndc5/Irisin and its signaling pathways.

Rabiee Farzaneh F Lachinani Liana L Ghaedi Sarvenaz S Nasr-Esfahani Mohammad Hossein MH Megraw Timothy L TL Ghaedi Kamran K

Cell & bioscience 20200330

Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects throu ...[more]

PMID: 32257109

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Project description:Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown. Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients. Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients. Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.

Dataset Information

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways.

Publications

New insights into the cellular activities of Fndc5/Irisin and its signaling pathways.

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