LINC00511 knockdown suppresses glioma cell malignant progression through miR-15a-5p/AEBP1 axis

Zhen Liu; Bei Tao; Linkun Li; Pin Liu; Kaiguo Xia; Chuanhong Zhong

doi:10.1016/j.brainresbull.2021.05.010

LINC00511 knockdown suppresses glioma cell malignant progression through miR-15a-5p/AEBP1 axis

Brain Res Bull. 2021 Aug:173:82-96. doi: 10.1016/j.brainresbull.2021.05.010. Epub 2021 May 13.

Authors

Zhen Liu¹, Bei Tao², Linkun Li¹, Pin Liu³, Kaiguo Xia⁴, Chuanhong Zhong⁵

Affiliations

¹ Neurosurgery Department, Nanyang Second General Hospital, China.
² Department of Rheumatology and Immunology, Affiliated Hospital of Southwest Medical University, China.
³ Science and Education Department, The Fourth People's Hospital of Nanyang, China.
⁴ Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, China; Sichuan Clinical Research Center for Neurosurgery, China; Laboratory of Neurological Diseases and Brain Function, China.
⁵ Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, China; Sichuan Clinical Research Center for Neurosurgery, China; Laboratory of Neurological Diseases and Brain Function, China. Electronic address: zhongchuanhong_zch@163.com.

PMID: 33992709
DOI: 10.1016/j.brainresbull.2021.05.010

Abstract

Background: A strong relationship between long intergenic non-protein coding RNA 511 (LINC00511) and glioma has been previously reported but the mechanism of LINC00511 in glioma is yet to be determined. This study examined the mechanism of LINC00511 in glioma.

Methods: The expression of LINC00511 in glioma was determined by bioinformatics analysis and real-time quantitative PCR (RT-qPCR) analysis. The target relationship between genes was predicted by starBase, TargetScan, and was verified by dual-luciferase. Subsequently, siRNA targeting LINC00511 (siLINC00511) and miR-15a-5p mimic were transfected into glioma cells to examine the effect on biological characteristics using cell counting kit-8, clone formation, flow cytometry, wound-healing, and transwell. MiR-15a-5p inhibitor and AEBP1 were used for in vitro rescue experiments, and tumorigenesis assay and immunohistochemical assays were performed for in vivo experiments. Epithelial-mesenchymal transition (EMT) and p65 phosphorylation were examined by Western blot.

Results: LINC00511 was predicted and verified to be up-regulated in glioma. SiLINC00511 suppressed cell viability, proliferation, migration and invasion, accelerated apoptosis of glioma cells. Mechanically, siLINC00511 promoted E-cadherin expression but suppressed N-cadherin and Snail expressions. MiR-15a-5p bound to LINC00511, and miR-15a-5p inhibitor partially reversed the effect and regulation of siLINC00511 on glioma cells. AEBP1, a target gene of miR-15a-5p, could activate p65 phosphorylation to promote EMT protein expression and partially reverse the inhibitory effect of miR-15a-5p mimic on the malignant phenotype of glioma cells. SiLINC00511 inhibited tumor growth, down-regulated miR-15a-5p expression and up-regulated AEBP1 and Ki67 expressions in vivo.

Conclusion: LINC00511 knockdown inhibits glioma cell progression via miR-15a-5p/AEBP1 axis.

Keywords: Adipocyte enhancer binding protein 1; Glioma; Long intergenic non-protein coding RNA 511; Malignant phenotype; miR-15a-5p.

Publication types

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

MeSH terms

Animals
Brain Neoplasms / genetics*
Brain Neoplasms / metabolism
Brain Neoplasms / pathology
Cell Line
Cell Movement / genetics
Cell Proliferation / genetics*
Computational Biology
Down-Regulation*
Epithelial-Mesenchymal Transition / genetics
Gene Knockdown Techniques
Glioma / genetics*
Glioma / metabolism
Glioma / pathology
Humans
Male
Mice
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism

Substances

RNA, Long Noncoding