TMEM17 Promotes Tumor Progression in Glioblastoma by Activating the PI3K/AKT Pathway.

BACKGROUND

Glioblastoma (GBM) is a highly aggressive and fast-growing brain tumor, characterized by rapid progression, a very poor prognosis, and a high likelihood of recurrence. Thus, effective new therapeutic targets are urgently needed. Transmembrane proteins (TMEMs) have pro-cancer effects on multiple cancer types, but the mechanisms underlying the effects of TMEM17, particularly its role in GBM, remain unclear.

METHODS

We conducted bioinformatics analyses and immunohistochemistry to evaluate the role of in a variety of cancer types. Functional assays were conducted included the Cell Counting Kit-8 assay, annexin V-FITC/PI double staining, 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay, wound healing assay, transwell invasion assay, and dual luciferase assay.

RESULTS

We found that is associated with a poor prognosis in GBM. Prognostic analyses confirmed that high expression predicted poorer survival, establishing its significance as an independent prognostic factor. Functional assays demonstrated that silencing in GBM cell lines inhibited proliferation and invasion, and induced apoptosis, underscoring its role in tumor aggressiveness. From a mechanistic perspective, we discovered that the Ying Yang 1 (YY1) transcription factor can bind to the promoter of , regulating its upregulation. Regarding downstream mechanisms, knocking down inhibited the phosphoinositide 3-kinase/AKT pathway. These findings suggest that plays a significant role in GBM and may be a potential therapeutic target for this cancer.

CONCLUSION

These data prove that plays a key role in the regulation of GBM and has great potential as a clinical therapeutic target for GBM.