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PRMT5 activates lipid metabolic reprogramming via MYC contributing to the growth and survival of mantle cell lymphoma.

Abstract
Mantle cell lymphoma (MCL) is an incurable and aggressive subtype of non-Hodgkin B-cell lymphoma. Increased lipid uptake, storage, and lipogenesis occur in a variety of cancers and contribute to rapid tumor growth. However, no data has been explored for the roles of lipid metabolism reprogramming in MCL. Here, we identified aberrant lipid metabolism reprogramming and PRMT5 as a key regulator of cholesterol and fatty acid metabolism reprogramming in MCL patients. High PRMT5 expression predicts adverse outcome prognosis in 105 patients with MCL and GEO database (GSE93291). PRMT5 deficiency resulted in proliferation defects and cell death by CRISPR/Cas9 editing. Moreover, PRMT5 inhibitors including SH3765 and EPZ015666 worked through blocking SREBP1/2 and FASN expression in MCL. Furthermore, PRMT5 was significantly associated with MYC expression in 105 MCL samples and the GEO database (GSE93291). CRISPR MYC knockout indicated PRMT5 can promote MCL outgrowth by inducing SREBP1/2 and FASN expression through the MYC pathway.
AuthorsJin-Hua Liang, Wei-Ting Wang, Rong Wang, Rui Gao, Kai-Xin Du, Zi-Wen Duan, Xin-Yu Zhang, Yue Li, Jia-Zhu Wu, Hua Yin, Hao-Rui Shen, Li Wang, Jian-Yong Li, Jin-Ran Guo, Wei Xu
JournalCancer letters (Cancer Lett) Vol. 591 Pg. 216877 (Jun 01 2024) ISSN: 1872-7980 [Electronic] Ireland
PMID38615930 (Publication Type: Journal Article)
CopyrightCopyright © 2024 Elsevier B.V. All rights reserved.
Topics
  • Lymphoma, Mantle-Cell (genetics, metabolism, pathology)
  • Humans
  • Protein-Arginine N-Methyltransferases (genetics, metabolism)
  • Proto-Oncogene Proteins c-myc (metabolism, genetics)
  • Lipid Metabolism
  • Cell Proliferation
  • Fatty Acid Synthase, Type I (metabolism, genetics)
  • Cell Line, Tumor
  • Sterol Regulatory Element Binding Protein 1 (metabolism, genetics)
  • Sterol Regulatory Element Binding Protein 2 (metabolism, genetics)
  • Gene Expression Regulation, Neoplastic
  • Animals
  • Mice
  • Male
  • Prognosis
  • Female
  • Cholesterol (metabolism)
  • CRISPR-Cas Systems
  • Metabolic Reprogramming

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