FLOT1, stabilized by WTAP/IGF2BP2 mediated N6-methyladenosine modification, predicts poor prognosis and promotes growth and invasion in gliomas

Tao Song; Zhongxu Hu; Chong Zeng; Haijun Luo; Jie Liu

doi:10.1016/j.heliyon.2023.e16280

FLOT1, stabilized by WTAP/IGF2BP2 mediated N6-methyladenosine modification, predicts poor prognosis and promotes growth and invasion in gliomas

Heliyon. 2023 May 25;9(6):e16280. doi: 10.1016/j.heliyon.2023.e16280. eCollection 2023 Jun.

Authors

Tao Song^{1

2

3}, Zhongxu Hu^{1

3}, Chong Zeng⁴, Haijun Luo⁵, Jie Liu⁵

Affiliations

¹ Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Department of Neurosurgery, Xiangya Jiangxi Hospital, Central South University, Nanchang, China.
³ National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Medicine, The Seventh Affiliated Hospital, Hengyang Medical School, University of South China, Changsha, China.
⁵ Department of Pathology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China.

Abstract

The expression, function, and mechanism of FLOT1 (flotillin-1) remains unknown in gliomas. Here, the expression and clinical value of FLOT1 in gliomas was bioinformatically and experimentally analyzed via online omics data and local tissues. Moreover, the effects of FLOT1 depletion on cell proliferation and invasion were also detected. Besides, the underlying roles of N6-methyladenosine modification (m6A) in FLOT1 upregulation was further explored. The results demonstrated that FLOT1 was significantly upregulated in gliomas and positively correlated with advanced progression and poor prognosis of patients. FLOT1 silencing notably suppressed the cell proliferation and invasion in gliomas. The expression of WTAP and IGF2BP2was positively correlated with FLOT1 expression and served as the writer and reader of FLOT1 m6A, respectively, which stabilized FLOT1 mRNA and maintained its upregulation in gliomas. Lastly, ectopic expression of FLOT1 could notably restore the inhibitory effects caused by WTAP and IGF2BP2 depletion in glioma cells. Collectively, our results originally confirmed the upregulation and oncogenic roles of FLOT1, and revealed that WTAP/IGF2BP2 mediated m6A contributed to the upregulation of FLOT1 in gliomas, highlighting the promising application of WTAP/IGF2BP2/FLOT1 axis in target treatment of gliomas.

Keywords: FLOT1; Gliomas; IGF2BP2; WTAP; m6A.