TIGAR (TP53 Induced Glycolysis Regulatory Phosphatase)

While ATP5A1 shows promise in tissue, plasma-based screening benefits from combining multiple markers, including pri-miR-526b. Further research is needed to refine plasma biomarker panels for effective early detection of breast cancer.

Mechanistically, TIGAR suppressed nigericin-triggered pyroptosis by preserving mitochondrial function and attenuating intracellular reactive oxygen species (ROS) accumulation. These findings supported the first evidence of TIGAR's regulatory role in the pyroptosis pathway in TNBC cells, offering a theoretical basis for targeting TIGAR as a novel therapeutic strategy for TNBC.

Here, we report the rational design of CuF16@246, an acid-responsive, dual-functional copper-based nanocoordination polymer that integrates Cu2+ and the p53 reactivator eprenetapopt (APR-246) within a single perfluorosebacic acid (PFSEA)-coordinated framework to synergistically induce cuproptosis and reverse tumor metabolic reprogramming...In vitro and in vivo studies demonstrate that CuF16@246 exhibits more efficient cellular uptake, more potent cytotoxicity, and more significant tumor growth inhibition than individual treatments, without inducing hemolysis or major organ toxicity. This work establishes a dual-functional strategy that combines metabolic reprogramming with sensitized cuproptosis, providing a promising framework for developing advanced copper-based nanomedicines for the treatment of mut-p53-positive cancers.

Collectively, this study highlights the critical role of TP53 target genes in the immediate response of TNBC cells to DNA-damaging agents like doxorubicin and etoposide. It also reveals distinct molecular mechanisms regulating their expression in resistant versus sensitive cells, offering potential therapeutic targets to improve treatment strategies for TNBC.

Two loci (SLIT3 rs1875972 and C12orf55 rs7137724) showed ancestry-specific heterogeneity, underscoring the role of population context. PRS analyses revealed robust associations with type 2 diabetes and sleep duration, linking aMT6s genetics to metabolic and circadian traits.These findings highlight context-dependent genetic architecture of melatonin metabolism and emphasize the importance of ancestry in interpreting biomarker GWAS.

This study has demonstrated that IV-delivery of a pegylated siRNA-biopolymer, TI6752, targeted against tigar mRNA transcripts, effectively inhibited tumor growth and angiogenesis in an HCT116 xenograft model of colorectal carcinoma. TI6752 could represent a effective therapeutic approach to target TIGAR's pro-oncogenic functions in human cancers.

Future investigations of minimally invasive CRC therapies should prioritize cellular proliferation, metabolic reprogramming, stress response, and apoptosis. Collectively, these findings establish a molecular foundation for precision surgery and provide novel insights into the CRC pathophysiology and iatrogenic organ damage mechanisms.

Our results indicated that TIGAR markedly inhibited glucose metabolism, ROS production, and susceptibility of lung cancer cells to cisplatin. Together, TIGAR plays a cancer-promoting role in lung cancer, which becomes a promising prognostic and therapeutic biomarker.

We also analyzed the correlation between TIGAR expression and immune infiltration and assessed its correlation with a clinical cohort of cervical cancer, and found that TIGAR expression was significantly associated with the infiltration levels of Foxp3 + Treg cells, CD11b + MDSC, CTLA4, and HAVCR2. TIGAR is a potential diagnostic and prognostic biomarker of cervical cancer and is expected to offer new possibilities for cervical cancer immunotherapy.

DC-Vesicles demonstrate structural resilience and functional retention across storage conditions. Their cold-chain-independent compatibility, immune-targeting profile, and potential regulatory classification as Non-New Chemical Entities (NCEs) support their advancement as candidates for precision immunotherapy in resistant solid tumors.

Our findings suggest that early activation of p53 is similarly protective against metabolic dysfunction-associated steatohepatitis and that redox control is an important mediator of this protection. Further studies evaluating the efficacy of proactive activation of p53 in the liver to prevent metabolic dysfunction-associated steatohepatitis, or administration of targeted antioxidants to augment p53 redox protection, could provide new treatment approaches for a condition with few approved therapies.

Preliminary studies suggest that combining TIGAR inhibition with the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) may offer a therapeutic strategy for AML...Single-cell RNA sequencing analysis also revealed that high TIGAR expression influences the glycolysis pathway, and correlates with markers of T cell exhaustion. This study indicates that blocking TIGAR prevents CD8+ T cell dysfunction and induces anti-AML immunity.