STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma DOI Open Access

Dongkwan Yoo,

Sichen Wu,

Seung‐Hyuk Choi

et al.

Molecules and Cells, Journal Year: 2024, Volume and Issue: unknown, P. 100145 - 100145

Published: Nov. 1, 2024

miR-454-3p has been reported to be a tumor suppressive micro-RNA (miRNA) in multiple cancer types. We identified the kinase STK33 mRNA, which is high-risk factor for survival neuroblastoma (NB) patients, as being substrate of NB. Even though an attractive target several cancers, development inhibitors challenging. For various cell lines tested, we demonstrated reduced growth and viability with mimic. From among candidate NB-associated miRNAs, mimic its antagonist had most profound effect on mRNA protein level changes. Under conditions external stress cells, RNA levels also negatively correlated. Luciferase reporter assays miR-454-3p, recombinant versions resistant significantly blunted established major functional miR-454-3p. Overexpression or knockdown promoted autophagy, at same time, increased apoptotic markers tested NB indicating mechanism agents. Given difficult-to-drug targets such recent successes delivery methods treatment, it thought that targeting cells miRNA STK33-dependent types may alternative means therapy.

Language: Английский

N-acetylglusosaminyl 1-phosphate transferase (GPT) is a facilitator in Bombyx mori Nucleopolyhedrovirus proliferation DOI

Xiaochun Jiang,

Huyan Meng,

Hailong Wei

et al.

Developmental & Comparative Immunology, Journal Year: 2025, Volume and Issue: 165, P. 105336 - 105336

Published: Feb. 7, 2025

Language: Английский

Citations

0
Sephin1 suppresses ER stress-induced cell death by inhibiting the formation of PP2A holoenzyme DOI Creative Commons
Satoshi Gojo, Daisuke Kami, Arata Sano

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 19, 2025

Abstract Sephin1 was discovered as a protein phosphatase inhibitor, and its efficacy against neurodegenerative diseases has been confirmed. There are conflicting reports on whether inhibition of eIF2α dephosphorylation by PP1 holoenzyme with the 1 regulatory subunit 15 A is mechanism action Sephin1. In present study, we found that significantly suppressed renal tubular cell death in an animal model ER stress administered tunicamycin. CHOP, which plays central role stress-induced pathway, requires nuclear translocation to act transcription factor increase expression death-related genes. markedly this CHOP. To elucidate molecular underlying suppressive effect Sephin1, used human epithelial cells under reduced intracellular CHOP levels promoting phosphorylation at Ser30, led degradation UPS. Phosphorylated generated Thr172-phosphorylated activated AMPK, increased phosphorylated AMPK. AMPK inactivated PP2A through Thr172, inhibits formation B isoform delta. These results indicate target experimental system.

Language: Английский

Citations

0
Spring viraemia of carp virus modulates the time-dependent unfolded protein response to facilitate viral replication DOI Creative Commons
Alex Romero, António Figueras, Beatriz Novoa

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 3, 2025

The spring viraemia of carp virus (SVCV) poses a significant threat to global aquaculture, yet effective antiviral drugs and vaccines remain unavailable. Understanding the interplay between host-pathogen interactions SVCV replication is crucial for devising preventive strategies. ZF4 cells were exposed UV-inactivated or live at different multiplicities infection, modulation unfolded protein response (UPR) was assayed by qPCR times. Moreover, treated with several UPR modulators investigate their effect on viral replication. also modulated in vivo zebrafish larvae, its impact survival against infection evaluated. This study reveals how exploits host's facilitate targets immunoglobulin heavy chain-binding (BiP) activating transcription factor 4 (ATF4) during early enhance RNA synthesis translation. At later stages, activation BiP, PKR-like ER kinase (PERK), inositol-requiring enzyme 1 alpha (IRE1α) pathways supports release progeny induces cellular processes, including immune responses apoptotic cell death. Furthermore, data demonstrate that modulating pathways, particularly ATF6 PERK, significantly affect replication, providing novel avenue drug development. Preliminary studies suggest feasibility chemically combat SVCV, though optimizing administration conditions maximize efficacy while minimizing side effects warrants further investigation. These findings offer critical insights into molecular mechanisms underlying pathogenesis highlight promising therapeutic intervention.

Language: Английский

Citations

0
Chimeras Derived from a P2Y14 Receptor Antagonist and UDP-Sugar Agonists for Potential Treatment of Inflammation DOI
Zhiwei Wen,

Asmita Pramanik,

Sarah A. Lewicki

et al.

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(10), P. 3255 - 3278

Published: Sept. 26, 2024

Tethered glycoconjugates of a naphthalene- and piperidine-containing antagonist the P2Y

Language: Английский

Citations

2
Enhancement of Triple-Negative Breast Cancer-Specific Induction of Cell Death by Silver Nanoparticles by Combined Treatment with Proteotoxic Stress Response Inhibitors DOI Creative Commons
Christina M. Snyder,

B. de Mateo,

Khushbu Patel

et al.

Nanomaterials, Journal Year: 2024, Volume and Issue: 14(19), P. 1564 - 1564

Published: Sept. 27, 2024

Metal nanoparticles have been tested for therapeutic and imaging applications in pre-clinical models of cancer, but fears toxicity limited their translation. An emerging concept nanomedicine is to exploit the inherent drug-like properties unmodified nanomaterials cancer therapy. To be useful clinically, there must a window between nanomaterial normal cells. This necessitates identification specific vulnerabilities cancers that can targeted using without inducing off-target toxicity. Previous studies point proteotoxic stress as driver silver nanoparticle (AgNPs) Two key cell responses involved mitigating proteotoxicity are heat shock response (HSR) integrated (ISR). Here, we examine role these play AgNP-induced cytotoxicity triple-negative breast (TNBC) immortalized mammary epithelial Furthermore, investigate HSR ISR inhibitors potential drug partners increase anti-cancer efficacy AgNPs increasing We showed did not strongly induce at transcriptional level, instead decreased expression proteins (HSPs) protein possibly due degradation AgNP-treated TNBC further inhibitor, KRIBB11, synergized with cells, also increased In contrast, found salubrinal, sustain pro-death signaling, enhanced death cells Subsequent co-culture demonstrated combination salubrinal selectively eliminated TNBCs affecting grown same well. Our findings provide additional support mechanism by which kill will help guide future efforts identify would beneficial use

Language: Английский

Citations

2
Altered N-linked glycosylation in depression: A pre-clinical study DOI

Yao Yang,

Yuan Li,

Wei-Di Wang

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 359, P. 333 - 341

Published: May 25, 2024

Language: Английский

Citations

0
STK33 as the functional substrate of miR-454-3p for suppression and apoptosis in neuroblastoma DOI Open Access

Dongkwan Yoo,

Sichen Wu,

Seung‐Hyuk Choi

et al.

Molecules and Cells, Journal Year: 2024, Volume and Issue: unknown, P. 100145 - 100145

Published: Nov. 1, 2024

miR-454-3p has been reported to be a tumor suppressive micro-RNA (miRNA) in multiple cancer types. We identified the kinase STK33 mRNA, which is high-risk factor for survival neuroblastoma (NB) patients, as being substrate of NB. Even though an attractive target several cancers, development inhibitors challenging. For various cell lines tested, we demonstrated reduced growth and viability with mimic. From among candidate NB-associated miRNAs, mimic its antagonist had most profound effect on mRNA protein level changes. Under conditions external stress cells, RNA levels also negatively correlated. Luciferase reporter assays miR-454-3p, recombinant versions resistant significantly blunted established major functional miR-454-3p. Overexpression or knockdown promoted autophagy, at same time, increased apoptotic markers tested NB indicating mechanism agents. Given difficult-to-drug targets such recent successes delivery methods treatment, it thought that targeting cells miRNA STK33-dependent types may alternative means therapy.

Language: Английский

Citations

0