PRNP (Prion Protein)

Across a CRC panel that included SNU-C5/WT and its 5-fluorouracil- and oxaliplatin-resistant derivatives, HT-29 (KRAS-wild-type), and HCT-8 and LoVo (KRAS-mutant), co-immunoprecipitation showed that PrPC forms complexes with the 37/67 kDa laminin receptor (RPSA), with PrPC-RPSA association particularly increased in KRAS-mutant HCT-8 and LoVo cells. Taken together, these findings suggest that extracellular PrPC supports RAS-AKT signaling, proliferation, and tumor-associated angiogenesis in KRAS-mutant colorectal cancer, and that PrPC neutralization additively enhances 5-fluorouracil activity in KRAS-mutant models. The data provide a preclinical basis for evaluating PrPC antibodies in combination with fluoropyrimidine-based regimens in patients with KRAS-mutant CRC.

It thus can serve as an indicator of tumor invasion, metastasis and prognosis. The knockout of PrPc inhibits growth and migration of tumor stem cells, revealing that PrPc may have the ability to promote the invasion and metastasis of colorectal cancer.

This study provides an overview of cancer-related EV research and identifies key directions for further mechanistic exploration and clinical translation of EVs in precision oncology.

This study demonstrates that PRNP is a key regulator of gemcitabine resistance in PDAC, modulating EMT, ferroptosis, and the tumor immune microenvironment. Targeting PRNP represents a promising therapeutic strategy to reverse gemcitabine resistance and may hold significant potential for clinical translation in PDAC treatment.

Collectively, our findings indicate that while PrPC facilitates early events in αS aggregate interaction with neurons, the sustained neurotoxicity induced by αS prefibrillar oligomers and fibrils is predominantly mediated by extracellular Ca2+. This promotes aggregate-membrane interactions, membrane permeabilization, and intracellular Ca2+ dyshomeostasis, thereby establishing a vicious cycle of neuronal dysfunction and death.

P=N/A, N=150, Recruiting, Massachusetts General Hospital | N=80 --> 150

FOXM1 and PRNP were experimentally evidenced to be highly expressed in meningioma cells, and their knockdown hindered cell growth and migration and triggered ROS accumulation. In summary, our findings established a novel oxidative stress-based molecular classification and identified potential treatment vulnerabilities in high-grade meningiomas, which might assist personalized clinical management.

P=N/A, N=80, Recruiting, Massachusetts General Hospital | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Jun 2027

An improved knowledge of these molecular mechanisms may reveal additional targets for cancer treatment. Further research is required to elucidate these mechanisms and to formulate targeted interventions.

According to the Gene Expression Profiling Interactive Analysis (GEPIA) database results, the target genes AFAP1L1, GPT2, PPP1R12B, PRNP and SGIP1 in the three-miRNA panel were good candidates. Our three-miRNA panel (hsa-miR-20b-5p, hsa-miR-200b-3p and hsa-miR-106a-5p) is anticipated to be a promising non-invasive biomarker for NPC screening and diagnosis.

CSF analysis revealed CSF-restricted MOG-IgG that became undetectable after corticosteroid therapy without clinical improvement. This case highlights the need for cautious interpretation of the CSF-restricted MOG-IgG in CJD.

The subsequent in vitro evaluation of digitoxigenin and oleandrin derivatives 13a, 13g, 15a, and 15gdemonstrated that these four analogs reduced steady-state ATP1A1 levels in T98G cells in the 12-96 nM range. Interestingly, only the oleandrin analog 15g also lowered also steady-state levels of the cellular prion protein (PrPC), the main therapeutic target for the treatment of prion diseases.