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Abstract Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is a member of the TIPE/TNFAIP8 family which regulates tumor growth and survival. Our goal is to delineate the detailed oncogenic role of TNFAIP8 in skin cancer development and progression. Here we demonstrated that higher expression of TNFAIP8 is associated with basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma development in patient tissues. Induction of TNFAIP8 expression by TNFα or by ectopic expression of TNFAIP8 in SCC or melanoma cell lines resulted in increased cell growth/proliferation. Conversely, silencing of TNFAIP8 decreased cell survival/cell migration in skin cancer cells. We also showed that miR-205-5p targets the 3′UTR of TNFAIP8 and inhibits TNFAIP8 expression. Moreover, miR-205-5p downregulates TNFAIP8 mediated cellular autophagy, increased sensitivity towards the B-RAF V600E mutant kinase inhibitor vemurafenib, and induced cell apoptosis in melanoma cells. Collectively our data indicate that miR-205-5p acts as a tumor suppressor in skin cancer by targeting TNFAIP8.
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This content will become publicly available on December 1, 2025
Overexpression of ELF3 in the PTEN-deficient lung epithelium promotes lung cancer development by inhibiting ferroptosis
Abstract Ferroptosis has been shown to play a crucial role in preventing cancer development, but the underlying mechanisms of dysregulated genes and genetic alternations driving cancer development by regulating ferroptosis remain unclear. Here, we showed that the synergistic role of ELF3 overexpression and PTEN deficiency in driving lung cancer development was highly dependent on the regulation of ferroptosis. HumanELF3(hELF3) overexpression in murine lung epithelial cells only caused hyperplasia with increased proliferation and ferroptosis. hELF3overexpression andPtengenetic disruption significantly induced lung tumor development with increased proliferation and inhibited ferroptosis. Mechanistically, we found it was due to the induction of SCL7A11, a typical ferroptosis inhibitor, and ELF3 directly and positively regulated SCL7A11 in the PTEN-deficient background. Erastin-mediated inhibition of SCL7A11 induced ferroptosis in cells with ELF3 overexpression and PTEN deficiency and thus inhibited cell colony formation and tumor development. Clinically, human lung tumors showed a negative correlation betweenELF3andPTENexpression and a positive correlation betweenELF3andSCL7A11in a subset of human lung tumors withPTEN-low expression.ELF3andSCL7A11expression levels were negatively associated with lung cancer patients’ survival rates. In summary, ferroptosis induction can effectively attenuate lung tumor development induced byELF3overexpression andPTENdownregulation or loss-of-function mutations.
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- Award ID(s):
- 2143673
- PAR ID:
- 10565388
- Author(s) / Creator(s):
- ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more »
- Publisher / Repository:
- Springer Nature
- Date Published:
- Journal Name:
- Cell Death & Disease
- Volume:
- 15
- Issue:
- 12
- ISSN:
- 2041-4889
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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