Cell Cycle-Related FAM64A Could be Activated by TGF-β Signaling to Promote Glioma Progression

Minjie Fu; Jingwen Zhang; Licheng Zhang; Yuan Feng; Xinqi Fang; Jinsen Zhang; Wenyu Wen; Wei Hua; Ying Mao

doi:10.1007/s10571-023-01348-2

Cell Cycle-Related FAM64A Could be Activated by TGF-β Signaling to Promote Glioma Progression

Cell Mol Neurobiol. 2023 Aug;43(6):2975-2987. doi: 10.1007/s10571-023-01348-2. Epub 2023 Apr 20.

Authors

Minjie Fu^#^{1

2

3

4

5}, Jingwen Zhang^#^{1

6}, Licheng Zhang^#^{1

2

3

4

5}, Yuan Feng^{1

2

3

4

5}, Xinqi Fang^{1

2

3

4

5}, Jinsen Zhang^{1

2

3

4

5}, Wenyu Wen^{1

2

3

4

5}, Wei Hua^{7

8

9

10

11}, Ying Mao^{12

13

14

15

16}

Affiliations

¹ Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
² National Center for Neurological Disorders, Beijing, China.
³ Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China.
⁴ Neurosurgical Institute of Fudan University, Shanghai, China.
⁵ Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
⁶ Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
⁷ Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. drhuawei@fudan.edu.cn.
⁸ National Center for Neurological Disorders, Beijing, China. drhuawei@fudan.edu.cn.
⁹ Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China. drhuawei@fudan.edu.cn.
¹⁰ Neurosurgical Institute of Fudan University, Shanghai, China. drhuawei@fudan.edu.cn.
¹¹ Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China. drhuawei@fudan.edu.cn.
¹² Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. maoying@fudan.edu.cn.
¹³ National Center for Neurological Disorders, Beijing, China. maoying@fudan.edu.cn.
¹⁴ Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China. maoying@fudan.edu.cn.
¹⁵ Neurosurgical Institute of Fudan University, Shanghai, China. maoying@fudan.edu.cn.
¹⁶ Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China. maoying@fudan.edu.cn.

^# Contributed equally.

PMID: 37081231
DOI: 10.1007/s10571-023-01348-2

Abstract

Gliomas are aggressive brain tumors characterized by uncontrolled cell proliferation. FAM64A, a cell cycle-related gene, has been found to promote cell proliferation in various tumors, including gliomas. However, the regulatory mechanism and clinical significance of FAM64A in gliomas remain unclear. In this study, we investigated FAM64A expression in gliomas with different grades and constructed FAM64A silenced cell lines to study its functions. Our results demonstrated that FAM64A was highly expressed in glioblastoma (P < 0.001) and associated with a poor prognosis (P < 0.001). Expression profiles at the single-cell resolution indicated FAM64A could play a role in a cell-cycle-dependent way to promote glioma cell proliferation. We further observed that FAM64A silencing in glioma cells resulted in disrupted proliferation and migration ability, and increased cell accumulation in the G2/M phase (P = 0.034). Additionally, TGF-β signaling upregulates FAM64A expression, and SMAD4 and FAM64A co-localize in high-grade glioma tissues. We found FAM64A knockdown inhibited TGF-β-induced epithelial-mesenchymal transition in glioma. Our findings suggest that FAM64A could serve as a diagnostic and therapeutic target in gliomas.

Keywords: Cell cycle; EMT; FAM64A; Glioma; Single-cell RNA-seq; TGF-β.

MeSH terms

Brain Neoplasms* / pathology
Cell Cycle / genetics
Cell Division
Cell Line, Tumor
Cell Movement / genetics
Cell Proliferation / genetics
Epithelial-Mesenchymal Transition / genetics
Gene Expression Regulation, Neoplastic
Glioma* / pathology
Humans
Transforming Growth Factor beta / metabolism

Substances

Transforming Growth Factor beta

Grants and funding

82072784/National Natural Science Foundation of China