BAY11-7082 Targets RNF25 to Reverse TRIP4 Ubiquitination-dependent NF-κB Activation and Apoptosis Resistance in Renal Cell Carcinoma.

NF-κB pathway dysregulation, a common driver of therapy resistance in cancer, promotes survival by suppressing apoptosis. While the anti-apoptotic role of NF-κB is recognized, the molecular mechanisms underlying this process remain poorly defined. Here, we identify the E3 ubiquitin ligase RNF25 as a key mediator of NF-κB-dependent apoptosis resistance in renal cell carcinoma cells, enabling evasion of multiple targeted therapies.

Splicing to keep splicing: A feedback system for cellular homeostasis and state transition.

Background: Alternative splicing (AS) plays a crucial role in regulating gene expression and governing proteomic diversity by generating multiple protein isoforms from a single gene. Increasing evidence has highlighted the regulation for pre-mRNA splicing of the splicing factors (SFs). This review aims to examine featured mechanisms and examples of SF regulation by AS, focusing on paradigmatic feedback loops and their biological implications.

Genome-Wide Identification of 109 NAC Genes and Dynamic Expression Profiles Under Cold Stress in .

(), a tropical tree valued for its medicinal, nutritional, and industrial applications, exhibits severe sensitivity to low-temperature stress in subtropical regions, particularly during seedling establishment. To address this challenge, this study systematically identified 109 NAC genes in and characterized their functional roles in cold adaptation via multi-omics analyses. All NAC proteins were hydrophilic.

Risk Stratification Prediction of Endometrial Cancer Using Microstructural Mapping Based on Time-Dependent Diffusion MRI.

Time-dependent diffusion MRI (t-dMRI) has potential in characterizing microstructural features; however, its value in imaging endometrioid endometrial adenocarcinoma (EEA) remains uncertain. Patients surgically confirmed with EEA were finally enrolled in our study. The t-dMRI data were acquired using pulsed gradient spin echo sequence and oscillating gradient spin echo sequences.

Blood pressure improvement after resection of non-functioning adrenal adenomas: influencing factors and serum metabolic features.

Introduction: Non-functioning adrenal adenomas (NFAs) are typically regarded as benign tumors that lack hormonal secretion. However, emerging evidence has shown that some patients with NFAs and hypertension experience improvements in blood pressure after adrenalectomy, indicating a potential correlation between NFAs and hypertension. Nevertheless, the precise mechanisms that underpin this phenomenon remain elusive.

USP7 depletion potentiates HIF2α degradation and inhibits clear cell renal cell carcinoma progression.

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo.

Discovery of a peptide proteolysis-targeting chimera (PROTAC) drug of p300 for prostate cancer therapy.

Background: The E1A-associated protein p300 (p300) has emerged as a promising target for cancer therapy due to its crucial role in promoting oncogenic signaling pathways in various cancers, including prostate cancer. This need is particularly significant in prostate cancer. While androgen deprivation therapy (ADT) has demonstrated promising efficacy in prostate cancer, its long-term use can eventually lead to the development of castration-resistant prostate cancer (CRPC) and neuroendocrine prostate cancer (NEPC).

A Top-Down Design Approach for Generating a Peptide PROTAC Drug Targeting Androgen Receptor for Androgenetic Alopecia Therapy.

While large-scale artificial intelligence (AI) models for protein structure prediction and design are advancing rapidly, the translation of deep learning models for practical macromolecular drug development remains limited. This investigation aims to bridge this gap by combining cutting-edge methodologies to create a novel peptide-based PROTAC drug development paradigm. Using ProteinMPNN and RFdiffusion, we identified binding peptides for androgen receptor (AR) and Von Hippel-Lindau (VHL), followed by computational modeling with Alphafold2-multimer and ZDOCK to predict spatial interrelationships.

Development of a PAK4-targeting PROTAC for renal carcinoma therapy: concurrent inhibition of cancer cell proliferation and enhancement of immune cell response.

Background: Finding the oncogene, which was able to inhibit tumor cells intrinsically and improve the immune answers, will be the future direction for renal cancer combined treatment. Following patient sample analysis and signaling pathway examination, we propose p21-activated kinase 4 (PAK4) as a potential target drug for kidney cancer. PAK4 exhibits high expression levels in patient samples and plays a regulatory role in the immune microenvironment.

Development of a Double-Stapled Peptide Stabilizing Both α-Helix and β-Sheet Structures for Degrading Transcription Factor AR-V7.

Peptide drugs offer distinct advantages in therapeutics; however, their limited stability and membrane penetration abilities hinder their widespread application. One strategy to overcome these challenges is the hydrocarbon peptide stapling technique, which addresses issues such as poor conformational stability, weak proteolytic resistance, and limited membrane permeability. Nonetheless, while peptide stapling has successfully stabilized α-helical peptides, it has shown limited applicability for most β-sheet peptide motifs.

PrLZ regulates EMT and invasion in prostate cancer via the TGF-β1/p-smad2/miR-200 family/ZEB1 axis.

Background: Prostate leucine zipper (PrLZ) is a prostate-specific protein, and our previous study demonstrated that PrLZ enhances the malignant progression of prostate cancer (Pca). However, the roles of PrLZ in epithelial to mesenchymal transition (EMT) remain unknown.

Methods: Quantitative real-time PCR (qRT-PCR), immunohistochemical (IHC) staining, hematoxylin-eosin (HE) staining, and western blotting were used to analyze the expression of protein and genes level in human PCa cell lines.

Knocking down AR promotes osteoblasts to recruit prostate cancer cells by altering exosomal circ-DHPS/miR-214-3p/CCL5 pathway.

Tumor-derived exosomes have been shown to play a key role in organ-specific metastasis, and the androgen receptor regulates prostate cancer (PCa) progression. It is unclear whether the androgen receptor regulates the recruitment of prostate cancer cells to the bone microenvironment, even bone metastases, through exosomes. Here, we found that exosomes isolated from PCa cells after knocking down androgen receptor (AR) or enzalutamide treatment can facilitate the migration of prostate cancer cells to osteoblasts.

EZH2-regulated immune risk score prognostic model predicts outcome of clear cell renal cell carcinoma.

Background: The enhancer of zeste homolog 2 (EZH2) plays an important role in the tumor microenvironment (TME), and EZH2 in shaping the epigenetic landscape of CD8 T cell fate and function, with a particular emphasis on cancer. Here, high EZH2 expression always leads to less CD8 T cell infiltration. However, clear cell renal cell carcinoma (ccRCC) is reportedly a "hot" tumor, with contradictory high EZH2 expression.

deletion stabilizes HIF1α to promote angiogenesis and glycolysis in prostate cancer.

Chromodomain-helicase-DNA-binding protein 1 (CHD1) deletion is among the most common mutations in prostate cancer (PCa), but its role remains unclear. In this study, RNA sequencing was conducted in PCa cells after clustered regularly interspaced palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9)-based CHD1 knockout. Gene set enrichment analysis (GSEA) indicated upregulation of hypoxia-related pathways.

De Novo Design of an Androgen Receptor DNA Binding Domain-Targeted peptide PROTAC for Prostate Cancer Therapy.

Androgen receptor splice variant-7 (AR-V7), one of the major driving factors, is the most attractive drug target in castration-resistant prostate cancer (CRPC). Currently, no available drugs efficiently target AR-V7 in clinical practice. The DNA binding domain (DBD) is indispensable for the transcriptional activity of AR full length and AR splice variants, including AR-V7.

CCL5-dependent mast cell infiltration into the tumor microenvironment in clear cell renal cell carcinoma patients.

We investigated the mechanisms affecting tumor progression and survival outcomes in -mutated () clear cell renal cell carcinoma (ccRCC) patients. ccRCC tissues contained higher numbers of mast cells and lower numbers of CD8 and CD4 T cells than tissues from ccRCC patients. Hierarchical clustering, pathway enrichment and GSEA analyses demonstrated that mutations promote tumor progression by activating hypoxia inducible factor (HIF)-related signaling pathways and increasing expression of vascular endothelial growth factor family genes.

Global, regional, and national burdens of bladder cancer in 2017: estimates from the 2017 global burden of disease study.

Background: The aim of this study is to describe the prevalence and mortality of bladder cancer (BCa) using data obtained in the Global Burden of Disease study performed in 2017 (GBD 2017).

Methods: Data on BCa for 2017, including prevalence, mortality, and disability-adjusted life years (DALYs), were obtained from GBD 2017 at the global, regional, and national levels. We also analyzed the association of BCa burden with the country development level.

Inhibition of Androgen Receptor Signaling Promotes Prostate Cancer Cell Migration via Upregulation of Annexin A1 Expression.

Background: Recent studies indicate that androgen deprivation therapy (ADT), the main therapeutic approach for metastatic prostate cancer (PCa), accelerates PCa invasion and metastasis. Annexin A1 (ANXA1) is a Ca-regulated phospholipid-binding protein that can promote PCa migration and invasion.

Aim Of The Study: The aim of this study is to determine whether ANXA1 is regulated by ADT and participates in PCa progression after ADT, and to explore the possible mechanism of ANXA1-mediated PCa migration.

Exosome-mediated miR-9-5p promotes proliferation and migration of renal cancer cells both in vitro and in vivo by targeting SOCS4.

Exosomes secreted by cancer cells play important roles in tumor progression by interacting with cell receptors. Renal cancer derived exosomes contain miRNAs which are associated with cell proliferation and invasion. Micro RNA 9-5 (miR-9-5) is highly expressed in the serum of renal cancer patients with advanced (tumor size - node - metastasis) TNM stage and Fuhrman grade.

Snail promotes prostate cancer migration by facilitating SPOP ubiquitination and degradation.

Prostate cancer (PCa) is the second leading cause of cancer-associated mortality in men. Speckle-type pox virus and zinc finger protein (SPOP), the most frequently mutated gene in PCa, functions as a tumor suppressor via degradation of cancer-promoting substrates. However, its upstream regulation in PCa metastasis remains poorly determined.

DARS-AS1 promotes clear cell renal cell carcinoma by sequestering miR-194-5p to up-regulate DARS.

Clear cell renal cell carcinoma (ccRCC), the most frequent subtype of renal cell carcinoma (RCC), is characterized by high relapse rate and mortality. Long non-coding RNAs (lncRNAs) are critical participants during cancer development. LncRNA DARS antisense RNA 1 (DARS-AS1), a newly-found lncRNA, is not specifically reported in ccRCC.