WP1066

RNF122 promotes glioblastoma growth via the JAK2/STAT3/c-Myc signaling Axis

**Objective:** E3 ubiquitin ligase has been identified as a key player in glioblastoma (GBM) progression and shows potential as a therapeutic target. This study investigates the role of E3 ubiquitin ligase RNF122 in GBM progression and the underlying molecular mechanisms.

**Methods:** RNF122 expression levels were assessed using qRT-PCR, Western blotting (WB), and immunohistochemistry (IHC). Functional assays and animal experiments were conducted to evaluate RNF122’s impact on GBM progression. Additionally, the effect of RNF122 on JAK2/STAT3/c-Myc signaling was examined using WB.

**Results:** RNF122 was found to be upregulated in GBM and associated with advanced disease stages and poor clinical outcomes, making it an independent prognostic factor. Functional assays demonstrated that RNF122 promotes GBM growth and cell cycle progression, which was further supported by its activation of the JAK2/STAT3/c-Myc pathway. The JAK2/STAT3 signaling pathway inhibitor WP1066 was able to mitigate the effects of RNF122 overexpression on GBM progression.

**Conclusion:** Our findings indicate that RNF122 contributes to an aggressive GBM phenotype and serves as a negative prognostic marker. Targeting RNF122 may be a promising approach for GBM treatment.