Cell death-inducing DFF45-like effector C intervenes the progression of non-small cell lung cancer via modulating lipid metabolism

Abstract

Background: The cell death-inducing DFF45-like (CIDE) effector family, plays a crucial role in lipid droplet formation and stability. Its N-terminal and C-terminal domains are closely linked to cell apoptosis and lipid droplet growth. However, the expression and functional role of CIDEC in non-small cell lung cancer (NSCLC) remain unexplored. This study aims to investigate the expression patterns and functional implications of CIDEC in NSCLC, with a particular focus on its role in lipid droplet metabolism and tumor progression.

Methods: We analyzed CIDEC expression levels in NSCLC tissues compared to normal lung tissues using immunohistochemistry and quantitative PCR. To elucidate the functional role of CIDEC, we performed in vitro and in vivo experiments involving overexpression and knockdown of CIDEC in NSCLC cell lines. Proliferation, invasion, and migration assays were conducted to assess the impact of CIDEC on tumor cell behavior. Additionally, lipid droplet morphology and triacylglycerol (TAG) content were evaluated using fluorescence microscopy and biochemical assays. The expression of ATGL, a downstream gene of CIDEC, was also measured to explore the mechanistic link between CIDEC and lipid droplet lipolysis.

Results: Our findings revealed that CIDEC expression was significantly downregulated in NSCLC tissues compared to normal tissues. Functionally, overexpression of CIDEC inhibited the proliferation, invasion, and migration of NSCLC cells both in vitro and in vivo. Furthermore, CIDEC overexpression led to an increase in lipid droplet diameter and TAG content, whereas CIDEC knockdown resulted in the reduction and fragmentation of large lipid droplets. Mechanistically, CIDEC deficiency was associated with increased ATGL expression and reduced lipid droplet content, while CIDEC overexpression correlated with elevated TAG levels and decreased ATGL protein levels. These results suggest that low CIDEC expression in NSCLC promotes tumor progression by enhancing ATGL-mediated lipolysis.

Conclusions: This study is the first to establish a link between CIDEC expression and lipid droplet lipolysis in NSCLC. Our findings indicate that CIDEC plays a critical role in regulating lipid metabolism and tumor progression in lung cancer. The downregulation of CIDEC in NSCLC promotes tumorigenesis by enhancing ATGL-induced lipolysis, highlighting CIDEC as a potential therapeutic target for lung cancer through metabolic reprogramming of lipid droplets. These insights provide a novel direction for targeted treatment strategies in NSCLC.

Keywords: apoptosis; cell death-inducing DFF45-like; lipid; non-small cell lung cancer.