Ubiquitin-specific proteases: From biological functions to potential therapeutic applications in gastric cancer

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116323 - 116323

Published: Feb. 23, 2024

Deubiquitination, a post-translational modification regulated by deubiquitinases, is essential for cancer initiation and progression. Ubiquitin-specific proteases (USPs) are elements of the deubiquitinase family, overexpressed in gastric (GC). Through regulation several signaling pathways, such as Wnt/β-Catenin nuclear factor-κB signaling, promotion expression deubiquitination- stabilization-associated proteins, USPs promote proliferation, metastasis, invasion, epithelial-mesenchymal transition GC. In addition, closely related to clinicopathological features, patient prognosis, chemotherapy resistance. therefore could be used prognostic biomarkers. USP targeting small molecule inhibitors have demonstrated strong anticancer activity. However, they not yet been tested clinic. This article provides an overview latest fundamental research on GC, aiming enhance understanding how contribute GC progression, identifying possible targets treatment improve survival.

Language: Английский

---

PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(7)

Published: July 15, 2023

Abstract PLAGL2 is upregulated in various tumors, including bladder cancer (BCa). However, the mechanisms underlying tumorigenic effects of BCa remain unclear. In our study, we proved that was overexpressed tissues and correlated with decreased survival. Functionally, deficiency significantly suppressed proliferation metastasis cells vitro vivo. RNA sequencing, qRT‒PCR, immunoblotting, immunofluorescence staining, luciferase reporter, ChIP assays revealed disrupted Hippo pathway increased YAP1/TAZ activity by transactivating RACGAP1. Further investigations demonstrated activated signaling via RACGAP1-mediated RhoA activation. Importantly, inhibitor simvastatin or verteporfin abrogated proproliferative prometastatic enhanced PLAGL2. These findings suggest promotes progression RACGAP1/RhoA GTPase/YAP1 signaling. Hence, core nodes may be promising therapeutic targets for BCa.

Language: Английский

---

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Cancer Medicine, Journal Year: 2024, Volume and Issue: 13(7)

Published: March 28, 2024

Abstract The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising methylation have been identified. Notably, these often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, complex roles human cancer pathology remain enigmatic, with conflicting outcomes reported different studies.In recent years, multitude inhibitors activators targeting reported. Several compounds demonstrated promising efficacy both vitro vivo models. These findings collectively underscore dynamic landscape regulation biology, revealing its potential therapeutic target indicator.

Language: Английский

---

Recent Advances in the Mutual Regulation of m6A Modification and Non-Coding RNAs in Atherosclerosis

International Journal of General Medicine, Journal Year: 2025, Volume and Issue: Volume 18, P. 1047 - 1073

Published: Feb. 1, 2025

Atherosclerosis, a progressive inflammatory disease of the arteries, remains leading cause cardiovascular morbidity and mortality worldwide. Recent years have witnessed pivotal role N6-methyladenosine (m6A) RNA methylation in regulating various biological processes, including those implicated atherosclerosis. Current evidence suggested that m6A regulators (writers, erasers, readers) participated modification multiple non-coding RNAs (ncRNAs), microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), thereby affecting their metabolism functions. Meanwhile, ncRNAs also emerged as key modulator expression turn. Therefore, understanding mutual regulation between modifications is great significance to identify novel therapeutic targets for atherosclerosis has clinical application prospects. This review aims summarize recent advances reciprocal provide insights into interaction context

Language: Английский

---

N6-methyladenosine RNA modification in stomach carcinoma: Novel insights into mechanisms and implications for diagnosis and treatment

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2025, Volume and Issue: 1871(5), P. 167793 - 167793

Published: March 14, 2025

Language: Английский

---

Tumor-Associated Fibroblast-Derived Exosomal circDennd1b Promotes Pituitary Adenoma Progression by Modulating the miR-145-5p/ONECUT2 Axis and Activating the MAPK Pathway

Cancers, Journal Year: 2023, Volume and Issue: 15(13), P. 3375 - 3375

Published: June 27, 2023

TAF participated in the progression of various cancers, including PA via release soluble factors. Exosomes belonged to extracellular vesicles, which were revealed as a crucial participator intercellular communication. However, expression pattern and effect TAF-derived exosomes remained largely unknown PA. In present study, we performed silico analysis based on public RNA-seq datasets generate circRNA/miRNA regulatory network. The qRT-PCR, Western blotting, RNA pull-down, luciferase assay investigate exosomes. exosomal circDennd1b was significantly upregulated promoted proliferation, migration, invasion cells sponging miR-145-5p cells. addition, directly regulated One Cut homeobox 2 (ONECUT2/OC2) inhibited promoting ONECUT2 We further demonstrated that transcriptionally increased fibroblast growth factor receptor 3 (FGFR3) expression, activates mitogen-activated protein kinases (MAPK) pathway, thus progression. Moreover, suppression TAFs by ABT-263 CSRM617 conclusion, our study illustrated affected regulating provides potential therapeutic strategy against aggressive

Language: Английский

---

Tectorigenin suppresses the viability of gastric cancer cells in vivo and in vitro

Quality Assurance and Safety of Crops & Foods, Journal Year: 2023, Volume and Issue: 15(3), P. 117 - 125

Published: Sept. 21, 2023

Gastric cancer is currently the 4th most common malignant tumor with a poor prognosis in 2022. New and effective drugs are needed to combat this disease treat advanced gastric cancer. Tectorigenin (Tec) has series of pharmacological activities, such as anti-inflammatory anticancer. However, effect Tec on progression unclear. In study, we investigated role regulating cell viability, cycle, growth To detect vitro mice, performed several assays MTT, colony formation, wound closure, transwell, Immunoblot assays, vivo assays. Our data confirmed that restrained viability cells at concentrations 100, 200, 300 μM. It also denied motility cells. treatment induced cycle arrest Mechanically, could suppress activation PI3K/Akt pathway stop progression. We, therefore, thought serve drug for treating

Language: Английский

---

Dysregulation of autophagy in gastric carcinoma: Pathways to tumor progression and resistance to therapy

Cancer Letters, Journal Year: 2024, Volume and Issue: 591, P. 216857 - 216857

Published: April 5, 2024

Language: Английский

---

LncRNA UCA1 promotes vasculogenic mimicry by targeting miR-1-3p in gastric cancer

Carcinogenesis, Journal Year: 2024, Volume and Issue: 45(9), P. 658 - 672

Published: May 14, 2024

Abstract Long noncoding RNA urothelial carcinoma-associated 1 (UCA1) has been implicated in several tumors. UCA1 promotes cell proliferation, migration, and invasion of gastric cancer (GC) cells, but the molecular mechanism not fully elucidated. This study revealed oncogenic effects on growth invasion. Furthermore, expression was significantly correlated with overall survival GC patients, clinicopathological indicators, including tumor size, depth invasion, lymph node metastasis, TNM stage. Additionally, miR-1-3p identified as a downstream target UCA1, which negatively regulated by UCA1. MiR-1-3p inhibited proliferation vasculogenic mimicry (VM), induced apoptosis upregulating BAX, BAD, suppressor TP53 levels. Moreover, almost completely reversed effect caused growth, VM formation. also confirmed that promoted vivo. In this study, we correlation between formation, is potentially crucial for metastasis. Meanwhile, its formation cells. summary, these findings indicate UCA1/miR-1-3p axis potential treatment.

Language: Английский

---

An imbalance between proliferation and differentiation underlies the development of microRNA-defective pineoblastoma

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 25, 2024

ABSTRACT Mutations in the microRNA processing genes DICER1 and DROSHA drive several cancers that resemble embryonic progenitors. To understand how microRNAs regulate tumorigenesis, we ablated Drosha or Dicer1 developing pineal gland to emulate pathogenesis of pineoblastoma, a brain tumor resembles undifferentiated precursors gland. Accordingly, these mice develop tumors marked by loss microRNAs, including let-7/miR-98-5p family, de-repression target genes. Pineal driven mimic Rb1 loss, as they exhibit upregulation S-phase homeobox transcription factors development. Blocking proliferation facilitates expression pinealocyte maturation markers, with concomitant reduction markers. Select markers remain elevated, however, normally repress absent. One such gene is oncofetal factor Plagl2 , which regulates pro-growth genes, inhibiting their signaling impairs growth. Thus, demonstrate may be therapeutically targeted downstream drivers proliferation.

Language: Английский

---