J Cancer 2021; 12(23):6989-7002. doi:10.7150/jca.63289 This issue

Research Paper

SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis

Wentao Li1#, Ismatullah Soufiany1#, Xiao Lyu1#, Chenfei Lu1, Yutian Wei1, Zhumei Shi1,2, Yongping You1,2✉

1. Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu, China.
2. Institute for Brain Tumors, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing 211166, Jiangsu, China.
#These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Li W, Soufiany I, Lyu X, Lu C, Wei Y, Shi Z, You Y. SP1-upregulated LBX2-AS1 promotes the progression of glioma by targeting the miR-491-5p/LIF axis. J Cancer 2021; 12(23):6989-7002. doi:10.7150/jca.63289. Available from https://www.jcancer.org/v12p6989.htm

File import instruction

Abstract

Graphic abstract

Background: Mounting evidences have shown the importance of lncRNAs in carcinogenesis and cancer progression. LBX2-AS1 is identified as an oncogenic lncRNA that is abnormally expressed in gastric cancer and lung cancer samples. This study aims to explore the potential role of LBX2-AS1 in regulating proliferation and EMT in glioma, and the underlying mechanism.

Methods: Relative levels of LBX2-AS1 in glioma samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on proliferation and EMT were examined in the xenograft glioma model and glioma cells. The interaction between SP1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene LIF was identified.

Results: LBX2-AS1 was upregulated in glioma samples and cell lines, and its transcription was promoted by binding to the transcription factor SP1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 sponge miR-491-5p to further upregulate LIF. The subsequent activated LIF/STAT3 signaling was responsible for promoting proliferation and EMT in glioma.

Conclusion: LBX2-AS1 is upregulated by SP1 in glioma, which promotes the progression of glioma by targeting the miR-491-5p/LIF axis. In view of this, LBX2-AS1 is suggested as a novel diagnostic biomarker and therapeutic target of glioma.

Keywords: LBX2-AS1, miR-491-5p, LIF, EMT, Glioma