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Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target

Abnormal energy metabolism, including enhanced aerobic glycolysis and lipid synthesis, is a well‐established feature of glioblastoma (GBM) cells. Thus, targeting the cellular glycolipid metabolism can be a feasible therapeutic strategy for GBM. This study aimed to evaluate the roles of MSI2, SNORD12...

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Autores principales: Dong, Weiwei, Liu, Xiaobai, Yang, Chunqing, Wang, Di, Xue, Yixue, Ruan, Xuelei, Zhang, Mengyang, Song, Jian, Cai, Heng, Zheng, Jian, Liu, Yunhui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114150/
https://www.ncbi.nlm.nih.gov/pubmed/34047477
http://dx.doi.org/10.1002/ctm2.411
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author Dong, Weiwei
Liu, Xiaobai
Yang, Chunqing
Wang, Di
Xue, Yixue
Ruan, Xuelei
Zhang, Mengyang
Song, Jian
Cai, Heng
Zheng, Jian
Liu, Yunhui
author_facet Dong, Weiwei
Liu, Xiaobai
Yang, Chunqing
Wang, Di
Xue, Yixue
Ruan, Xuelei
Zhang, Mengyang
Song, Jian
Cai, Heng
Zheng, Jian
Liu, Yunhui
author_sort Dong, Weiwei
collection PubMed
description Abnormal energy metabolism, including enhanced aerobic glycolysis and lipid synthesis, is a well‐established feature of glioblastoma (GBM) cells. Thus, targeting the cellular glycolipid metabolism can be a feasible therapeutic strategy for GBM. This study aimed to evaluate the roles of MSI2, SNORD12B, and ZBTB4 in regulating the glycolipid metabolism and proliferation of GBM cells. MSI2 and SNORD12B expression was significantly upregulated and ZBTB4 expression was significantly low in GBM tissues and cells. Knockdown of MSI2 or SNORD12B or overexpression of ZBTB4 inhibited GBM cell glycolipid metabolism and proliferation. MSI2 may improve SNORD12B expression by increasing its stability. Importantly, SNORD12B increased utilization of the ZBTB4 mRNA transcript distal polyadenylation signal in alternative polyadenylation processing by competitively combining with FIP1L1, which decreased ZBTB4 expression because of the increased proportion of the 3′ untranslated region long transcript. ZBTB4 transcriptionally suppressed the expression of HK2 and ACLY by binding directly to the promoter regions. Additionally, ZBTB4 bound the MSI promoter region to transcriptionally suppress MSI2 expression, thereby forming an MSI2/SNORD12B/FIP1L1/ZBTB4 feedback loop to regulate the glycolipid metabolism and proliferation of GBM cells. In conclusion, MSI2 increased the stability of SNORD12B, which regulated ZBTB4 alternative polyadenylation processing by competitively binding to FIP1L1. Thus, the MSI2/SNORD12B/FIP1L1/ZBTB4 positive feedback loop plays a crucial role in regulating the glycolipid metabolism of GBM cells and provides a potential drug target for glioma treatment.
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spelling pubmed-81141502021-05-18 Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target Dong, Weiwei Liu, Xiaobai Yang, Chunqing Wang, Di Xue, Yixue Ruan, Xuelei Zhang, Mengyang Song, Jian Cai, Heng Zheng, Jian Liu, Yunhui Clin Transl Med Research Articles Abnormal energy metabolism, including enhanced aerobic glycolysis and lipid synthesis, is a well‐established feature of glioblastoma (GBM) cells. Thus, targeting the cellular glycolipid metabolism can be a feasible therapeutic strategy for GBM. This study aimed to evaluate the roles of MSI2, SNORD12B, and ZBTB4 in regulating the glycolipid metabolism and proliferation of GBM cells. MSI2 and SNORD12B expression was significantly upregulated and ZBTB4 expression was significantly low in GBM tissues and cells. Knockdown of MSI2 or SNORD12B or overexpression of ZBTB4 inhibited GBM cell glycolipid metabolism and proliferation. MSI2 may improve SNORD12B expression by increasing its stability. Importantly, SNORD12B increased utilization of the ZBTB4 mRNA transcript distal polyadenylation signal in alternative polyadenylation processing by competitively combining with FIP1L1, which decreased ZBTB4 expression because of the increased proportion of the 3′ untranslated region long transcript. ZBTB4 transcriptionally suppressed the expression of HK2 and ACLY by binding directly to the promoter regions. Additionally, ZBTB4 bound the MSI promoter region to transcriptionally suppress MSI2 expression, thereby forming an MSI2/SNORD12B/FIP1L1/ZBTB4 feedback loop to regulate the glycolipid metabolism and proliferation of GBM cells. In conclusion, MSI2 increased the stability of SNORD12B, which regulated ZBTB4 alternative polyadenylation processing by competitively binding to FIP1L1. Thus, the MSI2/SNORD12B/FIP1L1/ZBTB4 positive feedback loop plays a crucial role in regulating the glycolipid metabolism of GBM cells and provides a potential drug target for glioma treatment. John Wiley and Sons Inc. 2021-05-12 /pmc/articles/PMC8114150/ /pubmed/34047477 http://dx.doi.org/10.1002/ctm2.411 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Dong, Weiwei
Liu, Xiaobai
Yang, Chunqing
Wang, Di
Xue, Yixue
Ruan, Xuelei
Zhang, Mengyang
Song, Jian
Cai, Heng
Zheng, Jian
Liu, Yunhui
Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title_full Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title_fullStr Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title_full_unstemmed Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title_short Glioma glycolipid metabolism: MSI2–SNORD12B–FIP1L1–ZBTB4 feedback loop as a potential treatment target
title_sort glioma glycolipid metabolism: msi2–snord12b–fip1l1–zbtb4 feedback loop as a potential treatment target
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114150/
https://www.ncbi.nlm.nih.gov/pubmed/34047477
http://dx.doi.org/10.1002/ctm2.411
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