Long non coding RNA SLC26A4-AS1 exerts antiangiogenic effects in human glioma by upregulating NPTX1 via NFKB1 transcriptional factor

Haijun Li; Raoyu Yan; Weiqing Chen; Xiaofei Ding; Jiaming Liu; Guang Chen; Qunfeng Zhao; Yiping Tang; Siye Lv; Shuangchun Liu; Ying Yu

doi:10.1111/febs.15325

Long non coding RNA SLC26A4-AS1 exerts antiangiogenic effects in human glioma by upregulating NPTX1 via NFKB1 transcriptional factor

FEBS J. 2021 Jan;288(1):212-228. doi: 10.1111/febs.15325. Epub 2020 Jul 15.

Authors

Haijun Li¹, Raoyu Yan², Weiqing Chen³, Xiaofei Ding⁴, Jiaming Liu⁵, Guang Chen⁴, Qunfeng Zhao⁶, Yiping Tang⁶, Siye Lv⁶, Shuangchun Liu⁶, Ying Yu⁷

Affiliations

¹ Department of Neurology, Taizhou Second People's Hospital, China.
² Ankang Ward, Taizhou Second People's Hospital, China.
³ Clinical Laboratory, Taizhou Women and Children Hospital, China.
⁴ Central Laboratory, Taizhou University Medical School, China.
⁵ School of Basic Medical Sciences, Wenzhou Medical University, China.
⁶ Blood Transfusion Division, Taizhou Municipal Hospital, China.
⁷ Infection Medicine, Taizhou Municipal Hospital, China.

PMID: 32255252
DOI: 10.1111/febs.15325

Abstract

Malignant gliomas are a heterogeneous group of brain tumors with a poor prognosis, which is largely due to its aggressive invasiveness and angiogenesis. In recent years, it has been found that multiple long noncoding RNAs (lncRNAs) participate in a wide range of biological functions including angiogenesis through the regulation of gene expression in cancers. In this study, we investigate and report the novel role of lncRNA SLC26A4-AS1 in gliomas, with a novel mechanism involving transcription factors NFKB1 and NPTX1. We determined that SLC26A4-AS1 was downregulated in human glioma tissues and cells. Furthermore, overexpression of SLC26A4-AS1 or NPTX1 restrained the aggressiveness of glioma cells and their pro-angiogenic ability. SLC26A4-AS1 was also found to upregulate NPTX1 by recruiting NFKB1 into the NPTX1 promoter. Moreover, silencing of either NPTX1 or NFKB1 restored the aggressive and pro-angiogenic properties of glioma cells in the presence of SLC26A4-AS1. Taken together, we demonstrate that SLC26A4-AS1 promotes NPTX1 transcriptional activity by recruiting NFKB1 and thus exerting antiangiogenic effects on glioma cells. This study provides an experimental basis for the intervention of SLC26A4-AS1 in the treatment of gliomas.

Keywords: NFKB1; NPTX1; SLC26A4-AS1; glioma; lncRNA.

Publication types

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

MeSH terms

Animals
Brain Neoplasms / blood supply
Brain Neoplasms / genetics*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
C-Reactive Protein / antagonists & inhibitors
C-Reactive Protein / genetics*
C-Reactive Protein / metabolism
Case-Control Studies
Cell Line, Tumor
Cell Movement
Cell Proliferation
Gene Expression Regulation, Neoplastic
Glioblastoma / blood supply
Glioblastoma / genetics*
Glioblastoma / metabolism
Glioblastoma / pathology
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
NF-kappa B p50 Subunit / antagonists & inhibitors
NF-kappa B p50 Subunit / genetics*
NF-kappa B p50 Subunit / metabolism
Neoplasm Grading
Neovascularization, Pathologic / genetics*
Neovascularization, Pathologic / metabolism
Neovascularization, Pathologic / pathology
Nerve Tissue Proteins / antagonists & inhibitors
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Neuroglia / metabolism
Neuroglia / pathology
Promoter Regions, Genetic
RNA, Long Noncoding / agonists
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Signal Transduction
Sulfate Transporters / genetics*
Sulfate Transporters / metabolism
Tumor Burden
Xenograft Model Antitumor Assays

Substances

NF-kappa B p50 Subunit
NFKB1 protein, human
Nerve Tissue Proteins
RNA, Long Noncoding
RNA, Small Interfering
SLC26A4 protein, human
Sulfate Transporters
neuronal pentraxin
C-Reactive Protein