YTHDF2 promotes anaplastic thyroid cancer progression by activating the DDIT4/AKT/mTOR signaling pathway DOI Creative Commons

Bao Dai,

Lei Xu, Shikuo Rong

и другие.

Biology Direct, Год журнала: 2024, Номер 19(1)

Опубликована: Ноя. 26, 2024

Abstract Background RNA methylation, an important reversible post-transcriptional modification in eukaryotes, has emerged as a prevalent epigenetic alteration. However, the role of m6A reader YTH domain family 2 (YTHDF2) not been reported anaplastic thyroid cancer (ATC) and its biological mechanism is unclear. Methods The relationship between YTHDF2 expression ATC was determined using data sets tissue samples. A range analytical techniques were employed to investigate regulatory ATC, including bioinformatics analysis, dot-blot methylated immunoprecipitation sequencing (MeRIP-seq), (RIP) assays, sequencing, stability assays dual luciferase reporter gene assays. In vitro vivo also conducted determine contribution development. Results significantly increased ATC. comprehensive experiments demonstrated that knockdown attenuated proliferation, invasion, migration, apoptosis promotion, whereas overexpression yielded opposite trend. Mechanistically, RNA-seq, MeRIP-seq RIP-seq molecular biology accelerated degradation DNA damage-inducible transcript 4 or regulated damage development 1 (DDIT4, REDD1) mRNA m6A-dependent manner, which turn activated AKT/mTOR signaling pathway induced activation epithelial-mesenchymal transition (EMT), thereby promoting tumor progression. Conclusions This study first demonstrate elevated levels suppress DDIT4 manner activate pathway, plays pivotal progression, it may serve promising therapeutic target future.

Язык: Английский

Invasion and metastasis in cancer: molecular insights and therapeutic targets DOI Creative Commons

Yongxing Li,

Fengshuo Liu,

Qingjin Cai

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 20, 2025

The progression of malignant tumors leads to the development secondary in various organs, including bones, brain, liver, and lungs. This metastatic process severely impacts prognosis patients, significantly affecting their quality life survival rates. Research efforts have consistently focused on intricate mechanisms underlying this corresponding clinical management strategies. Consequently, a comprehensive understanding biological foundations tumor metastasis, identification pivotal signaling pathways, systematic evaluation existing emerging therapeutic strategies are paramount enhancing overall diagnostic treatment capabilities for tumors. However, current research is primarily metastasis within specific cancer types, leaving significant gaps our complex cascade, organ-specific tropism mechanisms, targeted treatments. In study, we examine sequential processes elucidate driving organ-tropic systematically analyze tumors, those tailored organ involvement. Subsequently, synthesize most recent advances technologies challenges opportunities encountered pertaining bone metastasis. Our objective offer insights that can inform future practice crucial field.

Язык: Английский

Процитировано

3
An update on promising and emerging protein kinase B/AKT inhibitors for breast cancer DOI Creative Commons

Riccardo Asnaghi,

Gabriele Antonarelli,

Elena Battaiotto

и другие.

Expert Opinion on Pharmacotherapy, Год журнала: 2025, Номер unknown

Опубликована: Янв. 23, 2025

Introduction . The PI3K pathway is crucial in breast cancer (BC), influencing cell survival, growth, and metabolism, with AKT playing a central role treatment resistance. This pathway's involvement carcinogenesis its link to resistance underscores the significance of targeting it BC therapy. PI3K-pathway inhibitors offer new therapeutic avenues but bring challenges, especially due toxicity issues that hinder their development.

Язык: Английский

Процитировано

1
A new peptide inhibitor of C1QBP exhibits potent anti‐tumour activity against triple negative breast cancer by impairing mitochondrial function and suppressing homologous recombination repair DOI Creative Commons
Xingxing Li, Yue Wu, Min Zhang

и другие.

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 1, 2025

Abstract C1QBP exhibits heightened expression across a spectrum of tumours, thereby fostering their proliferation and metastasis, rendering it pivotal therapeutic target. Nevertheless, to date, no pharmacological agents capable directly targeting inducing the degradation have been identified. In this study, we unveiled new peptide, PDBAG1, derived from precursor protein GPD1, employing peptidomics‐based drug screening strategy. PDBAG1 has demonstrated substantial efficacy in suppressing triple‐negative breast cancer (TNBC) both vitro vivo. Its mechanism action involves mitochondrial impairment inhibition oxidative phosphorylation (OXPHOS), achieved through direct binding C1QBP, promoting its ubiquitin‐dependent degradation. Concomitantly, due metabolic adaptability, observed an up‐regulation glycolysis compensate for OXPHOS inhibition. We aberrant phenomenon wherein hypoxia signalling pathway tumour cells exhibited significant activation under normoxic conditions following treatment. Through size‐exclusion chromatography (SEC) isothermal titration calorimetry (ITC) assays, validated that is with K d value 334 nM. Furthermore, inhibits homologous recombination repair proteins facilitates synergism poly‐ADP‐ribose polymerase inhibitors therapy. This underscores ultimately induces insurmountable survival stress multiple mechanisms while concurrently engendering vulnerabilities specific TNBC. Key points The newly discovered peptide first small molecule substance found target degrade demonstrating inhibitory effects potential.

Язык: Английский

Процитировано

0
FASN inhibition shows the potential for enhancing radiotherapy outcomes by targeting glycolysis, AKT, and ERK pathways in breast cancer DOI Creative Commons
Ching-I Chen,

Deng-Yu Kuo,

Hui-Yen Chuang

и другие.

International Journal of Radiation Biology, Год журнала: 2025, Номер unknown, С. 1 - 12

Опубликована: Янв. 10, 2025

Purpose Breast cancer ranks as the most prevalent in women, characterized by heightened fatty acid synthesis and glycolytic activity. Fatty synthase (FASN) is prominently expressed breast cells, regulating synthesis, thereby enhancing tumor growth migration, leading to radioresistance. This study aims investigate how FASN inhibition affects cell proliferation, radioresistance cancer, well mechanisms involved.

Язык: Английский

Процитировано

0
Anticancer Effects of MAPK6 siRNA‐Loaded PLGA Nanoparticles in the Treatment of Breast Cancer DOI Creative Commons
Ceyhun Toruntay, Fatma Şayan Poyraz, Seda Süsgün

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(2)

Опубликована: Янв. 1, 2025

ABSTRACT siRNA‐loaded nanoparticles open new perspectives for cancer treatment. MAPK6 is upregulated in breast and involved cell growth, differentiation cycle regulation. Herein, we aimed to investigate the anticancer effects of knockdown by using PLGA (siMAPK6‐PLGA‐NPs) MCF‐7 cells. After synthesis characterisation nanoparticles, treatment concentrations were determined with cytotoxicity assay. Subsequently, siMAPK6‐PLGA‐NPs evaluated vitro assays. have been suppress expression efficiently. In studies revealed that significantly reduced migration, proliferation colony‐forming ability enhanced apoptosis Taken together, exhibited robust promising against Our findings demonstrated great potential gene may be therapeutic target cancer.

Язык: Английский

Процитировано

0
Smurf2 Suppresses Proliferation and Cell Cycle of Triple‐Negative Breast Cancer Cells by Promoting the Polyubiquitination and Degradation of RPL35A DOI Creative Commons

Siyu Wei,

Yuying Liu, Zhihao Wang

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(2)

Опубликована: Янв. 1, 2025

ABSTRACT Human L35a ribosomal protein (RPL35A) has been reported to confer higher drug resistance and viability triple‐negative breast cancer (TNBC) cells, but the mechanism related its promotion of TNBC malignant progression is still unclear. Here, we found that silencing RPL35A could inhibit proliferation cells by suppressing G1/S phase transition. Furthermore, SMAD‐specific E3 ubiquitin ligase 2 (Smurf2) was be a potential upstream RPL35A. Smurf2 interact with promote degradation K63‐linked polyubiquitination, thereby transition cells. In addition, roles were confirmed in xenograft mouse model. Finally, negative correlation between levels human tissues. summary, inhibits blocking cell cycle process, which associated regulating

Язык: Английский

Процитировано

0
The Purinergic Ligand‐Gated Ion Channel 7 Receptor Promotes the Proliferation, Invasion, and Migration of Breast Cancer Cells DOI
Xin Wang, Xiaoxiang Peng,

Yahui Cao

и другие.

Journal of Biochemical and Molecular Toxicology, Год журнала: 2025, Номер 39(2)

Опубликована: Фев. 1, 2025

ABSTRACT Purinergic ligand‐gated ion channel 7 receptor (P2X7R) has essential functions in tumor proliferation, apoptosis, metastasis, and invasion, the purpose of this study was to explore effects P2X7R on biological behaviors MCF‐7 MDA‐MB‐231 cells. A bioinformatics analysis expression breast cancer performed its relationships with overall survival immune cell infiltration were determined. function detected via a Fluo‐4‐AM assay. Proliferation, migration invasion investigated using CCK‐8, scratch wound healing, Transwell assays, respectively. The levels P2X7R, JNK, p‐JNK, Akt, p‐Akt, E‐cadherin, N‐cadherin, vimentin GAPDH by western blotting. role cells vivo. Bioinformatics revealed an obvious increase differences observed among different subtypes. High negatively correlated affected infiltration. experimental results that both types express functional P2X7R. ATP BzATP can promote metastasis after activation; upregulate N‐cadherin vimentin; downregulate E‐cadherin compared control group, addition antagonist A438079 or oxATP knockdown could weaken these effects. activation their behaviors, indicating is latent therapeutic target cancer.

Язык: Английский

Процитировано

0
Increasing RB1 Expression by Targeting EZH2 in Triple‐Negative Breast Cancer DOI Creative Commons

Rui Yang,

Liyan Fei, Yingfei Xue

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(5)

Опубликована: Март 1, 2025

ABSTRACT Loss of RB1 function represents a defining characteristic triple‐negative breast cancer (TNBC) and is intricately associated with resistance to therapeutic interventions. In this study, we investigate the epigenetic mechanisms governing expression in TNBC. Employing combination bioinformatics analyses experimental validations, identified lysine histone methyltransferase EZH2 as key upstream regulator expression. primarily mediates trimethylation 27 on H3 catalytic subunit Polycomb repressive complex 2 (PRC2) complex. Furthermore, our findings demonstrate that pharmacological inhibition leads significant upregulation levels, mediated by enhanced enrichment activating marker H3K27ac at enhancer region, evidenced ATAC‐sequencing ChIP‐qPCR assays. These insights unveil promising clinical avenue for combating RB1‐mediated drug TNBC through strategic integration epigenetic‐targeting agents.

Язык: Английский

Процитировано

0
Pseudostellaria heterophylla (Miq.) Pax, a Traditional Folk Medicine, Ameliorates Colorectal Cancer by Remodeling the Tumor Immune Microenvironment DOI
Gui Yang, Hui Wu, Heng Fan

и другие.

Journal of Ethnopharmacology, Год журнала: 2025, Номер 342, С. 119362 - 119362

Опубликована: Янв. 17, 2025

Язык: Английский

Процитировано

0
Improved Efficacy of Triple‐Negative Breast Cancer Immunotherapy via Hydrogel‐Based Co‐Delivery of CAR‐T Cells and Mitophagy Agonist DOI Creative Commons
Guodong Li,

Ruoxin Du,

Donghui Wang

и другие.

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 22, 2025

Leaky and structurally abnormal blood vessels increased pressure in the tumor interstitium reduce infiltration of CAR-T cells solid tumors, including triple-negative breast cancer (TNBC). Furthermore, high burden may cause reduction infiltrating their functional exhaustion. In this study, various effector-to-target (E:T) ratio experiments are established to model treatment using leukemia (high E:T ratio) (low ratio). It is found that antitumor immune response decreased tumors with low ratio. single cell sequencing performed investigate exhaustion at a revealed inhibition mitophagy-mediated mitochondrial dysfunction diminished efficacy CAR-T-cell therapy. The mitophagy agonist BC1618 screened via AI-deep learning cytokine detection, vivo vitro studies significantly strengthened improving mitophagy. Here, injection hydrogels engineered for controlled co-delivery improves TNBC. Local delivery creates an inflammatory mitophagy-enhanced microenvironment site, which stimulates proliferation, provides ability persistently, effect treatment.

Язык: Английский

Процитировано

0