NPC1 (NPC Intracellular Cholesterol Transporter 1)

LEPR affected NK cell membrane cholesterol levels by influencing the CAMKK-SREBP1-HMGCR cholesterol endogenous synthesis pathway and regulating the expression of NPC1 and NPC2 genes, which ultimately influencing NK cell cytotoxic function. The study is significant for understanding the mechanism of NK cell activity in microgravity and offers new targets for clinical immunotherapy of NK cells.

This study reveals that NPC1 may be a potential therapeutic target for the treatment of human cancers.

Functional enrichment analysis of the top 50 positively correlated genes with NPC1 highlighted significant enrichment in pathways related to organelle fission, nuclear division, chromosomal region spindle formation, and centrosome function, suggesting a role for NPC1 in DNA replication processes. These findings establish a correlation between NPC1 expression and HCC prognosis, laying the groundwork for future studies to explore the therapeutic potential of NPC1 inhibition in HCC.

Positive correlations of NPC1 protein with tumor size and negative associations with tumor inflammation were observed only in women. This study showed that hepatocyte NPC1 protein levels are highly elevated in HCC tissue in both sexes but are more closely associated with survival in male patients than in female patients.

These observations are further reinforced by a comprehensive analysis of clinical databases alongside immunohistochemistry findings. In conclusion, our research suggests that NPC1's overexpression could contribute to hepatocellular carcinoma progression by promoting neutrophil recruitment, positioning NPC1 as a promising new biomarker and therapeutic target for hepatocellular carcinoma.

Overall, our results strongly indicate that the inhibition of NPC1 suppresses liver cancer cell proliferation. Targeting NPC1 is a promising potential therapeutic strategy for liver cancer.

NPC1 expression is upregulated in GC and serves as a pivotal prognostic factor for adverse outcomes in GC patients.

We strongly believe that a cell-specific rescue may not be sufficient to counteract the severity of the NPC pathology, but targeting common mechanisms, such as endo-lysosomal and lipid trafficking dysfunction, may ameliorate NPC pathology. This article is part of a discussion meeting issue 'Understanding the endo-lysosomal network in neurodegeneration'.

Expression of NPC1 is increased in ccRCC at mRNA and protein levels, and high expression of NPC1 is associated with poor prognosis. Our current findings show that ccRCC cells are particularly sensitive to the inhibition of endolysosomal cholesterol export and underline the therapeutic potential of targeting NPC1 in ccRCC.

As opposed to the normal dendritic localization of melanosomes, the disruption of melanosome matrix generation in NPC1 deficient cells causes an accumulation of immature melanosomes adjacent to the plasma membrane.. Together with the melanosomal localization of NPC1 in wild type cells, these findings suggest that NPC1 is directly involved in tyrosinase transport from the trans-Golgi network (TGN) to melanosomes and melanosome maturation, indicating a novel function for NPC1.

The ability to obtain cholesterol as a byproduct of increased macropinocytosis allows cancer cells to direct the resources needed for the energy-consuming cholesterol synthesis towards other activities such as invasion. These results demonstrate that macropinocytosis is not only an alternative energy source for cancer cells but also an efficient way to provide building material, such as cholesterol, for its macromolecules and membranes.

This study helped to identify new prognostic markers and potential immunotherapeutic targets for LIHC and revealed the molecular mechanisms underlying NPC1 regulation in LIHC. The NPCs play a key role in the prognosis and diagnosis of LIHC and may be an important indicator for LIHC prognosis and diagnosis; NPC1 might be a potential therapeutic target in LIHC.