2. Academic Validation
  3. ZC3H15 promotes glioblastoma progression through regulating EGFR stability

ZC3H15 promotes glioblastoma progression through regulating EGFR stability

  • Cell Death Dis. 2022 Jan 13;13(1):55. doi: 10.1038/s41419-021-04496-9.
Jianbing Hou 1 2,  Minghao Xu 1 2,  Hongyu Gu 1 2,  Dakun Pei 1 2,  Yudong Liu 1 2,  Pan Huang 1 2,  Hongbo Chang 1 2,  Hongjuan Cui 3 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Silkworm Genome Biology, Southwest University, 400716, Chongqing, China.
  • 2 Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, 400716, Chongqing, China.
  • 3 State Key Laboratory of Silkworm Genome Biology, Southwest University, 400716, Chongqing, China. [email protected].
  • 4 Cancer Center, Reproductive Medicine Center, Medical Research Institute, Southwest University, 400716, Chongqing, China. [email protected].
PMID: 35027542 DOI: 10.1038/s41419-021-04496-9
Abstract

Zinc finger CCCH-type containing 15 (ZC3H15), a highly conserved protein involved in several cellular processes, which was responsible for tumorigenesis and may be a promising marker in myeloid leukemia (AML) and hepatocellular carcinoma (HCC). However, little is known about the biological significance and molecular mechanisms of ZC3H15 in GBM. In this study, we revealed that ZC3H15 was overexpressed in GBM and high ZC3H15 expression was associated with poor survival of patients with GBM. We found that ZC3H15 promoted the proliferation, migration, invasion, and tumorigenesis of GBM cells by activating the EGFR signaling pathway. We also revealed that ZC3H15 reduced EGFR ubiquitination, which was responsible for EGFR protein stabilization. In addition, we demonstrated that ZC3H15 inhibited the transcription of CBL, which was an E3 ubiquitin ligase for EGFR proteasomal degradation. And silencing of CBL could partly abrogate the inhibitory effects on cell proliferation, migration, and invasion of GBM cells induced by ZC3H15 knockdown. Thus, our research revealed the important roles of ZC3H15 in GBM development and provided a brand-new insight for improving the treatment of GBMs.

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