HOTAIRM1 Maintained the Malignant Phenotype of tMSCs Transformed by GSCs via E2F7 by Binding to FUS

Liang Liu; Yanling Zhou; Xuchen Dong; Suwen Li; Shan Cheng; Haoran Li; Yongdong Li; Jiaqi Yuan; Liping Wang; Jun Dong

doi:10.1155/2022/7734413

HOTAIRM1 Maintained the Malignant Phenotype of tMSCs Transformed by GSCs via E2F7 by Binding to FUS

J Oncol. 2022 May 9:2022:7734413. doi: 10.1155/2022/7734413. eCollection 2022.

Authors

Liang Liu¹, Yanling Zhou¹, Xuchen Dong¹, Suwen Li¹, Shan Cheng¹, Haoran Li¹, Yongdong Li¹, Jiaqi Yuan¹, Liping Wang¹, Jun Dong¹

Affiliation

¹ Department of Neurosurgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China.

Abstract

Objective: Mesenchymal stromal/stem cells (MSCs) are an important part of the glioma microenvironment and are involved in the malignant progression of glioma. In our previous study, we showed that MSCs can be induced to a malignant phenotype (tMSCs) by glioma stem cells (GSCs) in the microenvironment. However, the potential mechanism by which tMSCs maintain their malignant phenotype after malignant transformation has not been fully clarified.

Methods: The expression of HOTAIRM1, FUS, and E2F7 was detected by qRT-PCR. Clone formation, EdU, and Transwell assay were used to explore the role of HOTAIRM1, FUS, and E2F7 on the proliferation, migration, and invasion of tMSCs. Bioinformatics analysis and RNA immunoprecipitation were used to explore the relation among HOTAIRM1, FUS, and E2F7.

Results: HOTAIRM1 was upregulated in tMSCs compared with MSCs. Loss- and gain-of-function assays showed that HOTAIRM1 promoted the proliferation, migration, and invasion of tMSCs. qRT-PCR and functional assays revealed that E2F7 might be the downstream target of HOTAIRM1. A further study of the mechanism showed that HOTAIRM1 could bind to FUS, an RNA-binding protein (RBP), and thus regulate E2F7, which could promote the malignant phenotype of tMSCs.

Conclusion: Our study revealed that the HOTAIRM1/FUS/E2F7 axis is involved in the malignant progression of tMSCs transformed by GSCs in the glioma microenvironment and may function as a novel target for glioma therapy.