MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase

Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRN...

Full description

Saved in:
Bibliographic Details
Main Authors: Zhenyang Liu, Junyu Wang, Yunjun Li, Juan Fan, Lihua Chen, Ruxiang Xu
Format: Article
Language:English
Published: SAGE Publishing 2017-02-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317691429
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849251238197067776
author Zhenyang Liu
Junyu Wang
Yunjun Li
Juan Fan
Lihua Chen
Ruxiang Xu
author_facet Zhenyang Liu
Junyu Wang
Yunjun Li
Juan Fan
Lihua Chen
Ruxiang Xu
author_sort Zhenyang Liu
collection DOAJ
description Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.
format Article
id doaj-art-a979b684ceb14819a73fee3c6559221d
institution Kabale University
issn 1423-0380
language English
publishDate 2017-02-01
publisher SAGE Publishing
record_format Article
series Tumor Biology
spelling doaj-art-a979b684ceb14819a73fee3c6559221d2025-08-20T03:57:00ZengSAGE PublishingTumor Biology1423-03802017-02-013910.1177/1010428317691429MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminaseZhenyang Liu0Junyu Wang1Yunjun Li2Juan Fan3Lihua Chen4Ruxiang Xu5Affiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, ChinaDepartment of Neurosurgery, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, ChinaAffiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, ChinaAffiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, ChinaAffiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, ChinaAffiliated Bayi Brain Hospital, General Hospital of Beijing Military Region, Beijing, ChinaGlioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis. We further found that microRNA-153 restrained glutamine utilization and glutamate generation. Bioinformatics analysis revealed that glutaminase, which catalyzed the formation of glutamate from glutamine, is the potential target of microRNA-153. Indeed, microRNA-153 cannot further reduce glutamine utilization when glutaminase was knocked down. Overexpression of glutaminase abrogates the effect of microRNA-153 on glutamine utilization. Furthermore, the relative expression of microRNA-153 and glutaminase in glioblastoma versus matched non-tumor tissues showed a reverse correlation, further indicating that microRNA-153 may negatively regulate glutaminase in vivo. These results demonstrate an unexpected role of microRNA-153 in regulating glutamine metabolism and strengthen the role of microRNA-153 as a therapeutic target in glioblastoma.https://doi.org/10.1177/1010428317691429
spellingShingle Zhenyang Liu
Junyu Wang
Yunjun Li
Juan Fan
Lihua Chen
Ruxiang Xu
MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
Tumor Biology
title MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
title_full MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
title_fullStr MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
title_full_unstemmed MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
title_short MicroRNA-153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
title_sort microrna 153 regulates glutamine metabolism in glioblastoma through targeting glutaminase
url https://doi.org/10.1177/1010428317691429
work_keys_str_mv AT zhenyangliu microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase
AT junyuwang microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase
AT yunjunli microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase
AT juanfan microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase
AT lihuachen microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase
AT ruxiangxu microrna153regulatesglutaminemetabolisminglioblastomathroughtargetingglutaminase