Specific Regulation of m<sup>6</sup>A by SRSF7 Promotes the Progression of Glioblastoma.

Yixian CUN; Sanqi AN; Haiqing ZHENG; Jing LAN; Wenfang CHEN; Wanjun LUO; Chengguo YAO; Xincheng LI; Xiang HUANG; Xiang SUN; Zehong WU; Yameng HU; Ziwen LI; Shuxia ZHANG; Geyan WU; Meisongzhu YANG; Miaoling TANG; Ruyuan YU; Xinyi LIAO; Guicheng GAO; Wei ZHAO; Jinkai WANG; Jun LI

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Specific Regulation of m⁶A by SRSF7 Promotes the Progression of Glioblastoma.

Author: Yixian CUN ¹ ; Sanqi AN ² ; Haiqing ZHENG ³ ; Jing LAN ⁴ ; Wenfang CHEN ⁵ ; Wanjun LUO ⁴ ; Chengguo YAO ⁶ ; Xincheng LI ¹ ; Xiang HUANG ⁵ ; Xiang SUN ⁵ ; Zehong WU ⁵ ; Yameng HU ¹ ; Ziwen LI ¹ ; Shuxia ZHANG ¹ ; Geyan WU ⁷ ; Meisongzhu YANG ¹ ; Miaoling TANG ⁷ ; Ruyuan YU ¹ ; Xinyi LIAO ¹ ; Guicheng GAO ⁵ ; Wei ZHAO ⁶ ; Jinkai WANG ⁸ ; Jun LI ⁹
Author Information

1. Department of Rehabilitation Medicine, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
2. Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Biosafety Level-3 Laboratory, Life Sciences Institute, Guangxi Medical University, Nanning 530020, China.
3. Department of Rehabilitation Medicine, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
4. Department of Obstetrics and Gynecology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
5. Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
6. Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China.
7. State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510080, China.
8. Department of Medical Informatics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: wangjk@mail.sysu.edu.cn.
9. Department of Rehabilitation Medicine, Key Laboratory of Liver Disease of Guangdong Province, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China; Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: lijun37@mail.sysu.edu.cn.
Publication Type:Journal Article
Keywords: Cell-specific regulation; Glioblastoma; PDZ-binding kinase; Serine/arginine-rich splicing factor 7; m(6)A
MeSH: Humans; Cell Line, Tumor; Cell Proliferation; Gene Expression Regulation, Neoplastic; Glioblastoma/genetics*; Methyltransferases/metabolism*; RNA Splicing Factors/metabolism*; RNA, Messenger/genetics*; RNA-Binding Proteins/metabolism*; Serine-Arginine Splicing Factors/metabolism*; RNA Methylation/genetics*
From: Genomics, Proteomics & Bioinformatics 2023;21(4):707-728
CountryChina
Language:English
Abstract: Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).

Specific Regulation of m6A by SRSF7 Promotes the Progression of Glioblastoma.

Specific Regulation of m⁶A by SRSF7 Promotes the Progression of Glioblastoma.