IL1RN mediates the suppressive effect of methionine deprivation on glioma proliferation

Kaikai Wang; Huailei Liu; Jiaqi Liu; Xiaoxiong Wang; Lei Teng; Jun Zhang; Yi Liu; Yizheng Yao; Jun Wang; Yuan Qu; Xin Chen; Fei Peng; Hongbo Liu; Ning Wang; Yingqiang Zhong; Xu Hou; Haiping Jiang; Ozal Beylerli; Xiang Liao; Xinjian Zhang; Xu Zhang; Xiangtong Zhang; Shiguang Zhao

doi:10.1016/j.canlet.2019.04.004

IL1RN mediates the suppressive effect of methionine deprivation on glioma proliferation

Cancer Lett. 2019 Jul 10:454:146-157. doi: 10.1016/j.canlet.2019.04.004. Epub 2019 Apr 10.

Authors

Kaikai Wang¹, Huailei Liu¹, Jiaqi Liu¹, Xiaoxiong Wang¹, Lei Teng¹, Jun Zhang¹, Yi Liu², Yizheng Yao², Jun Wang², Yuan Qu², Xin Chen¹, Fei Peng³, Hongbo Liu⁴, Ning Wang¹, Yingqiang Zhong¹, Xu Hou¹, Haiping Jiang¹, Ozal Beylerli⁵, Xiang Liao⁶, Xinjian Zhang¹, Xu Zhang¹, Xiangtong Zhang⁷, Shiguang Zhao⁸

Affiliations

¹ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.
² Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02215, USA.
³ Department of Neurosurgery, The Second Affiliated Hospital and Institute of Neurosciences of Guangzhou Medical University, Guangzhou, 510260, China.
⁴ College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, Heilongjiang Province, China.
⁵ Bashkir State Medical University, Ufa, 450008, Russia.
⁶ Department of Medical Imaging, General Hospital of Nanjing Military Area Command, Nanjing, 210002, Jiangsu Province, China.
⁷ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. Electronic address: xiangtongzhang@hotmail.com.
⁸ Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China; Institute of Neuroscience, Sino-Russian Medical Research Center, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. Electronic address: guangsz@hotmail.com.

PMID: 30978442
DOI: 10.1016/j.canlet.2019.04.004

Abstract

Metabolic abnormality is one of the hallmarks of cancer cells, and limiting material supply is a potential breakthrough approach for cancer treatment. Increasing researchers have been involved in the study of glioma cell metabolism reprogramming since the significance of IDH1 was confirmed in glioma. However, the molecular mechanisms underlying metabolic reprogramming induced by methionine deprivation regulates glioma cell proliferation remain unclear. Here we demonstrated that methionine deprivation inhibited glioma cell proliferation via downregulating interleukin 1 receptor antagonist (IL1RN) both in vitro and in vivo, methionine deprivation or knocking down IL1RN induced glioma cell cycle arrest. Moreover, we confirmed that IL1RN is a tumor associated gene and its expression is negatively correlated with the survival time of glioma patients. Altogether these results demonstrate a strong rationale insight that targeting amino acid metabolism such as methionine deprivation/IL1RN related gene therapy may offer novel direction for glioma treatment.

Keywords: Gene therapy; Glioma; IL1RN; Metabolic reprogramming; Tumor associated gene.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain Neoplasms / metabolism*
Brain Neoplasms / pathology
Cell Line, Tumor
Cell Proliferation / physiology
Down-Regulation
Glioma / metabolism*
Glioma / pathology
Heterografts
Humans
Interleukin 1 Receptor Antagonist Protein / biosynthesis*
Interleukin 1 Receptor Antagonist Protein / genetics
Methionine / deficiency*
Mice
Mice, Inbred BALB C
Mice, Nude
RNA, Messenger / genetics
RNA, Messenger / metabolism
Transfection

Substances

IL1RN protein, human
Interleukin 1 Receptor Antagonist Protein
RNA, Messenger
Methionine