APH1A (Aph-1 Homolog A, Gamma-Secretase Subunit)

The consistent alterations suggest the presence of a shared Notch-driven oncogenic signature in breast cancer, potentially driving cell proliferation, stemness, and resistance to therapy. These findings enhance our understanding of Notch signaling in breast cancer and propose novel miRNA-Notch interactions as candidate targets for therapeutic intervention.

Kyoto Encyclopedia of Genes and Genomes analyses showed that the 157 upregulated genes were mainly enriched in gastric acid secretion, Mitogen-activated protein kinase signaling pathway, etc, and the 171 downregulated genes were mainly enriched in transcriptional misregulation in cancer, Tumor necrosis factor signaling pathway, etc. The overexpression of PPIA in human umbilical vein endothelial cells causes changes in the expression of downstream genes and induces alternative splicing in multiple genes. PPIA alters the expression or the alternative splicing pattern of downstream genes, leading to pathogenesis of vascular endothelial injury by high glucose mediated through CyPA.

In summary, our study indicated that genetically proxied metformin effects may be associated with an increased risk of prostate cancer. Repurposing metformin for prostate cancer prevention in general populations is not supported by our findings.

Collectively, our current study strongly suggests that miR-138-2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138-2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.

hBN-NPs also suppressed the remarkable elevation in the signal for Aβ following exposure to Aβ for 48 h. Our results indicated that hBN-NPs could significantly prevent the neurotoxic damages by Aβ. Thus, hBN-NPs could be a novel and promising anti-AD agent for effective drug development, bio-nano imaging or drug delivery strategies.