RNASET2 (Ribonuclease T2)

Animal experiments indicate that Ctsa knockdown effectively enhances ICB efficacy on PDAC. Our study uncovers a VAT-EV CTSA-pseudouridine-mast cell axis connecting obesity and cancer, which holds promise for developing new therapeutic strategies for obesity-related cancers.

By combining in-cell stable isotope incorporation assay with quantitative metabolomics we show: cellular uptake of external purines and their internal generation are equivalent; an upregulation in lysosome biogenesis that functions in response to purine deficiency caused by methotrexate (MTX) and lometrexol (LTX) treatment. This leads to increased RNA digestion as visualized by a newly developed intracellular RNA-FRET oligo assay. Interestingly, downregulation of lysosomal RNase activity through knockdown of RNAseT2 increased RNA accumulation and a compensating increase in DNPB.

Finally, silencing of RNASET2 in THP-1 macrophages unveiled their phagocytic activities against PCa cells. Our findings underscore the RNASET2's dual functionality, acting through both cell-autonomous and non-cell autonomous mechanisms in PCa in vitro and in vivo models and suggest its potential as a therapeutic target in a subset of PCa.

Genes and biological and molecular pathways associated with hallmarks of aging were in mitochondria-dependent oxidative phosphorylation and reactive oxygen species synthesis, ER-dependent stress and unfolded protein response, DNA repair (UV response and P53 signaling pathways), and senescence, glycolysis and apoptosis regulation through PI3K-AKT-mTOR signaling have been shown to play important roles in aging or neurodegeneration (such as Parkinson's and Alzheimer's disease). We propose that the downregulation of TMEM230 and RNASET2 may represent a paradigm for the study of age-dependent autoimmune disorders due to their role in regulating glycosylation, unfolded protein response, and PI3K-AKT-mTOR signaling.

In summary, we conducted a multi-omic studies, which integrated three levels to investigate the novel targets for LC. Through a series of verifications, RNASET2 was identified as the key gene for LC in the current research.

However, the deficiency of RNASET2-induced HCC metastasis can be reversed by blocking MET with shRNA or savolitinib...Its deficiency drives HCC metastasis through cholesterol-triggered MET activation. These findings highlight the potential of targeting RNASET2 and MET in improving the prognosis of HCC.

Therefore, PTGES2 and RNASET2 are highlighted as effective biomarkers and therapeutic targets for BCC within the phenome-wide human disease category. The study identifies PTGES2 and RNASET2 plasma proteins as novel, reliable biomarkers and therapeutic targets for BCC, suggesting more effective clinical application strategies for patients.

Combined with animal component free culture media, non-biogenic scaffolds are suitable for proteomic and glycobiological analyses to identify human factors in aging. Applications of electrospun nanofiber technologies in 3D cell culture allow for ex situ screening and the development of patient personalized therapeutic strategies and predicting their effectiveness in mitigating or promoting aging.

Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis.

Our proteome-wide MR analysis highlighted RNASET2, TFPI, VWC2, NTM, and FLT1 as potential drug targets for further clinical investigation in LUAD. However, the specific mechanisms by which these proteins influence LUAD remain elusive. Targeting these proteins in drug development holds the potential for successful clinical trials, providing a pathway to prioritize and reduce costs in LUAD therapeutics.

In vitro experiments reveal that this accumulation results in increased cell proliferation, potentially from altered metabolic pathways. RNASET2 exhibits a tumor-promoting role in the pathogenesis of ccRCC that is increased in the presence of a specific RNASET2-SV and associated with changes in the cellular localization of the protein.

Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.