Colorectal cancer (CRC) is widely prevalent and represents a significant contributor to global cancer‑related mortality. There remains a pressing demand for advancements in CRC treatment modalities. The E3 ubiquitin ligase is a critical enzyme involved in modulating protein expression levels via posttranslational ubiquitin‑mediated proteolysis, and it is reportedly involved in the progression of various cancers, making it a target of recent interest in anticancer therapy. In the present study, using comprehensive expression analysis involving spatial transcriptomic analysis with single‑cell RNA sequencing in clinical CRC datasets, the ubiquitin‑associated protein Shank‑associated RH domain interactor () was identified, located on amplified chromosome 8q, which could promote CRC progression. was found to be upregulated in tumor cells, with elevated expression observed in tumor tissues. This heightened expression of was positively associated with lymphatic invasion and served as an independent predictor of a poor prognosis in patients with CRC. and analyses using SHARPIN‑overexpressing or ‑knockout CRC cells revealed that SHARPIN overexpression upregulated MDM2, resulting in the downregulation of p53, while SHARPIN silencing or knockout downregulated MDM2, leading to p53 upregulation, which affects cell cycle progression, tumor cell apoptosis and tumor growth in CRC. Furthermore, was found to be overexpressed in several cancer types, exerting significant effects on survival outcomes. In conclusion, SHARPIN represents a newly identified novel gene with the potential to promote tumor growth following apoptosis inhibition and cell cycle progression in part by inhibiting p53 expression via MDM2 upregulation; therefore, SHARPIN represents a potential therapeutic target for CRC.
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http://dx.doi.org/10.3892/ijo.2024.5701 | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Key Laboratory of Cryogenics Science and Technology, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Sublethal tumor cells have an urgent need for energy, making it common for them to switch metabolic phenotypes between glycolysis and oxidative phosphorylation (OXPHOS) for compensatory energy supply; thus, the synchronous interference of dual metabolic pathways for limiting energy level is essential in inhibiting sublethal tumor growth. Herein, a multifunctional nanoplatform of Co-MOF-loaded anethole trithione (ADT) and myristyl alcohol (MA), modified with GOx and hyaluronic acid (HA) was developed, namely, CAMGH. It could synchronously interfere with dual metabolic pathways including glycolysis and OXPHOS to restrict the adenosine triphosphate (ATP) supply, achieving the inhibition to sublethal tumors after microwave (MW) thermal therapy.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
January 2025
Department of Urology, Affiliated Xi'an Peoples Hospital (Xi'an Fourth Hospital) of Northwest University, Xi'an, 710000, China.
Limited treatment options are available for bladder cancer (BCa) resulting in extremely high mortality rates. Cyclovirobuxine D (CVB-D), a naturally alkaloid, reportedly exhibits notable antitumor activity against diverse tumor types. However, its impact on CVB-D on BCa and its precise molecular targets remain unexplored.
View Article and Find Full Text PDFClin Exp Med
January 2025
Department of Hematology-Oncology, Imam Hossein Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
IL-27 is structurally an immune-enhancing and pleiotropic two-chain cytokine associated with IL-12 and IL-6 families. IL-27 contains two subunits, namely IL-27p28 and EBI3. A heterodimer receptor of IL-27, composed of IL27Rα (WSX1) and IL6ST (gp130) chains, mediates the IL-27 function following the activation of STAT1 and STAT3 signaling pathways.
View Article and Find Full Text PDFEur Geriatr Med
January 2025
Department of Public Health, Jining Medical University, Jining, 272000, China.
Purpose: Sarcopenia is an age-related disease that is related to nutritional intake and chronic low-grade inflammation. The aim of this study was to investigate the association of dietary intake, inflammatory markers and sarcopenia among the community-dwelling older adults.
Methods: A total of 1001 older adults aged 60 and above were recruited.
ACS Appl Mater Interfaces
January 2025
Key Laboratory of Functional Polymer Materials of Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.
CRISPR/Cas9 (CRISPR, clustered regularly interspaced short palindromic repeats) gene editing technology represents great promise for treating glioblastoma (GBM) due to its potential to permanently eliminate tumor pathogenic genes. Unfortunately, delivering CRISPR to the GBM in a safe and effective manner is challenging. Herein, a glycosylated and cascade-responsive nanoparticle (GCNP) that can effectively cross the blood-brain barrier (BBB) and activate CRISPR/Cas9-based gene editing only in the GBM is designed.
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