m5C modification of LINC00324 promotes angiogenesis in glioma through CBX3/VEGFR2 pathway

Aini Pan; Yixue Xue; Xuelei Ruan; Weiwei Dong; Di Wang; Yunhui Liu; Libo Liu; Yang Lin; Tiange E; Hongda Lin; Hailing Xu; Xiaobai Liu; Ping Wang

doi:10.1016/j.ijbiomac.2023.128409

m5C modification of LINC00324 promotes angiogenesis in glioma through CBX3/VEGFR2 pathway

Int J Biol Macromol. 2024 Feb;257(Pt 1):128409. doi: 10.1016/j.ijbiomac.2023.128409. Epub 2023 Nov 26.

Authors

Aini Pan¹, Yixue Xue¹, Xuelei Ruan¹, Weiwei Dong², Di Wang², Yunhui Liu², Libo Liu¹, Yang Lin¹, Tiange E², Hongda Lin², Hailing Xu², Xiaobai Liu³, Ping Wang⁴

Affiliations

¹ Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.
² Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.; Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
³ Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.; Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: [email protected].
⁴ Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang 110122, China; Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang 110004, China.. Electronic address: [email protected].

PMID: 38016610
DOI: 10.1016/j.ijbiomac.2023.128409

Abstract

Angiogenesis plays a major role in tumor initiation, progression, and metastasis. This is why finding antiangiogenic targets is essential in the treatment of gliomas. In this study, NSUN2 and LINC00324 were significantly upregulated in conditionally cultured glioblastoma endothelial cells (GECs). Knockdown of NSUN2 or LINC00324 inhibits GECs angiogenesis. NSUN2 increased the stability of LINC00324 by m5C modification and upregulated LINC00324 expression. LINC00324 competes with the 3'UTR of CBX3 mRNA to bind to AUH protein, reducing the degradation of CBX3 mRNA. In addition, CBX3 directly binds to the promoter region of VEGFR2, enhances VEGFR2 transcription, and promotes GECs angiogenesis. These findings demonstrated NSUN2/LINC00324/CBX3 axis plays a crucial role in regulating glioma angiogenesis, which provides new strategies for glioma therapy.

Keywords: 5-methylcytosine; Angiogenesis; CBX3; Glioma; LINC00324; NSUN2.

MeSH terms

Angiogenesis
Cell Proliferation / genetics
Chromosomal Proteins, Non-Histone
Endothelial Cells* / metabolism
Glioma* / pathology
Humans
RNA, Messenger / genetics

Substances

RNA, Messenger
CBX3 protein, human
Chromosomal Proteins, Non-Histone