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

Abstract

BackgroundFAM64A has been found to promote tumor cell proliferation in various tumors. However, the regulatory mechanism and clinical signi cance of FAM64A in gliomas still remain unclear. MethodsFAM64A expression in gliomas with different grades was determined by TCGA database mining and immunoblotting assay. FAM64A silenced U87 cells were constructed with shRNA, and cell proliferation, migration, and cell cycle and were detected by CCK8 assay, scratch assay, and ow cytometry respectively. Intercellular crosstalk analysis and transcription factor prediction were performed to query the potential regulatory mechanisms. TGF-b and its downstream transcription factors were detected in glioma samples with different grades to validate the regulatory roles of TGF-b signaling. ResultsFAM64A was highly expressed in glioblastoma and associated with a poor prognosis. FAM64A silenced U87 cell lines displayed disrupted proliferation and migration ability. More cells would be stuck in the S phase. Expression pro les at the single-cell resolution further indicated that FAM64A could play a role in a cell-cycle-dependent way to promote the proliferation of glioma cells. FAM64A expression could be induced by TGF-β signal. And colocalization of SMAD4 and FAM64A could be observed in high-grade glioma tissues. ConclusionsFAM64A could serve as a malignant biomarker in gliomas, and it could be induced via TGF-β pathway activation., which could explain the crosstalk between glioma cells and also the microenvironment.