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Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma

Icaritin is a potential treatment option for hepatocellular carcinoma (HCC) based on the results of its phase 2 stage trial. Glucose transporter 1 (GLUT1), a critical gene in regulating glycolysis, has been recognized as a promising target in HCC treatment. Previous studies have reported that FAM99A...

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Autores principales: Zheng, Xia, Gou, Yudong, Jiang, Ziyu, Yang, Aizhen, Yang, Zhihui, Qin, Shukui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576446/
https://www.ncbi.nlm.nih.gov/pubmed/34765550
http://dx.doi.org/10.3389/fonc.2021.740557
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author Zheng, Xia
Gou, Yudong
Jiang, Ziyu
Yang, Aizhen
Yang, Zhihui
Qin, Shukui
author_facet Zheng, Xia
Gou, Yudong
Jiang, Ziyu
Yang, Aizhen
Yang, Zhihui
Qin, Shukui
author_sort Zheng, Xia
collection PubMed
description Icaritin is a potential treatment option for hepatocellular carcinoma (HCC) based on the results of its phase 2 stage trial. Glucose transporter 1 (GLUT1), a critical gene in regulating glycolysis, has been recognized as a promising target in HCC treatment. Previous studies have reported that FAM99A, a new long noncoding (lncRNA), is associated with HCC metastasis. It has also been demonstrated that the JAK2/STAT3 pathway is related to HCC and is the target of icaritin treatment. However, whether FAM99A participates in icaritin treatment and regulates GLUT1-mediated glycolysis via the JAK2/STAT3 pathway in HCC cells remains to be explored. Our study aimed to clarify the mechanisms underlying glycolysis and understand the regulating effects of the FAM99A and JAK2/STAT3 pathway in HCC cells in icaritin treatment. Molecular mechanism studies were conducted to verify whether FAM99A could bind to the JAK2/STAT3 pathway and to identify the regulatory mechanisms in the HCC cells. It was revealed that icaritin inhibited proliferation, GLUT1 level, and the glycolysis of the HCC cells. FAM99A in HCC cells was upregulated after a high concentration treatment of icaritin. FAM99A inhibited GLUT1 by blocking the JAK2/STAT3 pathway. Mechanically, FAM99A interacted with EIF4B to inhibit gp130 and gp80 translation, which then interacted with miR-299-5p to upregulate SOCS3, causing the JAK2 pathway to inhibit STAT3 phosphorylation, so that JAK2/STAT3 was blocked in HCC cells. Overall, our study proved that icaritin-induced FAM99A can inhibit HCC cell viability and GLUT1-mediated glycolysis via blocking the JAK2/STAT3 pathway.
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spelling pubmed-85764462021-11-10 Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma Zheng, Xia Gou, Yudong Jiang, Ziyu Yang, Aizhen Yang, Zhihui Qin, Shukui Front Oncol Oncology Icaritin is a potential treatment option for hepatocellular carcinoma (HCC) based on the results of its phase 2 stage trial. Glucose transporter 1 (GLUT1), a critical gene in regulating glycolysis, has been recognized as a promising target in HCC treatment. Previous studies have reported that FAM99A, a new long noncoding (lncRNA), is associated with HCC metastasis. It has also been demonstrated that the JAK2/STAT3 pathway is related to HCC and is the target of icaritin treatment. However, whether FAM99A participates in icaritin treatment and regulates GLUT1-mediated glycolysis via the JAK2/STAT3 pathway in HCC cells remains to be explored. Our study aimed to clarify the mechanisms underlying glycolysis and understand the regulating effects of the FAM99A and JAK2/STAT3 pathway in HCC cells in icaritin treatment. Molecular mechanism studies were conducted to verify whether FAM99A could bind to the JAK2/STAT3 pathway and to identify the regulatory mechanisms in the HCC cells. It was revealed that icaritin inhibited proliferation, GLUT1 level, and the glycolysis of the HCC cells. FAM99A in HCC cells was upregulated after a high concentration treatment of icaritin. FAM99A inhibited GLUT1 by blocking the JAK2/STAT3 pathway. Mechanically, FAM99A interacted with EIF4B to inhibit gp130 and gp80 translation, which then interacted with miR-299-5p to upregulate SOCS3, causing the JAK2 pathway to inhibit STAT3 phosphorylation, so that JAK2/STAT3 was blocked in HCC cells. Overall, our study proved that icaritin-induced FAM99A can inhibit HCC cell viability and GLUT1-mediated glycolysis via blocking the JAK2/STAT3 pathway. Frontiers Media S.A. 2021-10-26 /pmc/articles/PMC8576446/ /pubmed/34765550 http://dx.doi.org/10.3389/fonc.2021.740557 Text en Copyright © 2021 Zheng, Gou, Jiang, Yang, Yang and Qin https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zheng, Xia
Gou, Yudong
Jiang, Ziyu
Yang, Aizhen
Yang, Zhihui
Qin, Shukui
Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title_full Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title_fullStr Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title_full_unstemmed Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title_short Icaritin-Induced FAM99A Affects GLUT1-Mediated Glycolysis via Regulating the JAK2/STAT3 Pathway in Hepatocellular Carcinoma
title_sort icaritin-induced fam99a affects glut1-mediated glycolysis via regulating the jak2/stat3 pathway in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576446/
https://www.ncbi.nlm.nih.gov/pubmed/34765550
http://dx.doi.org/10.3389/fonc.2021.740557
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