IFI35 Promotes Renal Cancer Progression by Inhibiting pSTAT1/pSTAT6-Dependent Autophagy.
Dafei ChaiShang Yuchen ShiNavid SobhaniJiage DingZichun ZhangNan JiangGang WangMinle LiHailong LiJunnian ZhengJin BaiPublished in: Cancers (2022)
Interferon-induced protein 35 (IFI35), is currently acknowledged to govern the virus-related immune inflammatory responses. However, the biological significance and function of IFI35 in renal cell cancer (RCC) is still not well understood. Here, IFI35 expression and function were investigated in RCC tissues, renal cancer cells, and animal models. The results showed that IFI35 expression was significantly increased in 200 specimens of RCC patients. We found that higher IFI35 levels were significantly correlated with poor RCC prognosis. In human cell lines, the knockdown of IFI35 suppressed the malignant behavior of renal cancer cells. Similarly, the IFI35 knockdown resulted in significant inhibition of tumor progression in the subcutaneous or lung metastasis mouse model. Furthermore, the knockdown of IFI35 promoted the induction of autophagy by enhancing the autophagy-related gene expression (LC3-II, Beclin-1, and ATG-5). Additionally, blockade of STAT1/STAT6 phosphorylation (pSTAT1/pSTAT6) abrogated the induced autophagy by IFI35 knockdown in renal cancer cells. The autophagy inhibitor 3-MA also abolished the prevention of tumor growth by deleting IFI35 in renal cancer models. The above results suggest that the knockdown of IFI35 suppressed tumor progression of renal cancer by pSTAT1/pSTAT6-dependent autophagy. Our research revealed that IFI35 may serve as a potential diagnosis and therapeutic target for RCC.
Keyphrases
- cell death
- signaling pathway
- gene expression
- papillary thyroid
- endoplasmic reticulum stress
- poor prognosis
- oxidative stress
- renal cell carcinoma
- mouse model
- squamous cell
- endothelial cells
- end stage renal disease
- diabetic rats
- stem cells
- newly diagnosed
- single cell
- squamous cell carcinoma
- dna methylation
- chronic kidney disease
- lymph node metastasis
- bone marrow
- climate change
- risk assessment
- immune response
- childhood cancer
- peritoneal dialysis
- human health
- protein kinase
- fine needle aspiration