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

Total flavonoids of litchi seed inhibit breast cancer metastasis by regulating the PI3K/AKT/mTOR and MAPKs signaling pathways DOI Creative Commons
Xin Yang,

Shoushi Liu,

Ying Liu

и другие.

Pharmaceutical Biology, Год журнала: 2025, Номер 63(1), С. 229 - 249

Опубликована: Апрель 15, 2025

Total flavonoids from Litchi chinensis Sonn. (Sapindaceae) seeds (TFLS) effectively attenuate stem cell-like properties in breast cancer cells. However, their pharmacological effects and mechanisms suppressing metastasis remain unclear. This study aimed to elucidate the inhibitory underlying of TFLS on metastasis. The antiproliferative, migratory, invasive activities cells following treatment were evaluated using CCK-8, wound-healing, transwell assays. epithelial-mesenchymal transition (EMT) biomarkers via Western blot analysis. anti-metastatic further validated vivo zebrafish mouse models. Network pharmacology methodology was utilized predict potential targets signaling pathways, which subsequently corroborated by blot. Potential active compounds identified through molecular docking, chemical constituents analyzed characterized UPLC-QTOF/MS. suppressed proliferation MDA-MB-231 MDA-MB-468 cells, with IC50 values 44.47 μg/mL 37.35 at 72 h, respectively. It vitro, demonstrated a marked reduction cellular motility invasiveness, alongside reversal EMT. Consistent pathway enrichment analysis, network revealed that reduced phosphorylation levels PI3K, AKT, mTOR, JNK, ERK, p38 Molecular docking seven ingredients, UPLC-MS/MS confirmed presence key compounds, including procyanidin A2. inhibits cell proliferation, migration, invasion vitro reversing EMT phenotype, while vivo. These are likely mediated attenuation PI3K/AKT/mTOR MAPK pathways.

Язык: Английский

Процитировано

0
Nanoconjugate Carrying pH-Responsive Transferrin Receptor-Targeted Hesperetin Triggers Triple-Negative Breast Cancer Cell Death through Oxidative Attack and Assemblage of Pro-Apoptotic Proteins DOI

Dibyendu Giri,

Surya Kanta Dey,

Sounik Manna

и другие.

ACS Applied Bio Materials, Год журнала: 2024, Номер 7(11), С. 7556 - 7573

Опубликована: Ноя. 6, 2024

Triple-negative breast cancer (TNBC) is recognized as a major aggressive subtype of due to its expeditious worsening growth, extensive metastatic capability, and recalcitrance standard current treatments. Hesperetin (HSP), natural bioflavonoid from citrus fruits, demonstrates pronounced anticancer efficacy, but hydrophobicity limits clinical development. The present study reports the fabrication biocompatible pH-responsive transferrin (TF) receptor-targeted HSP-loaded poly(lactic-co-glycolic acid) (PLGA) nanobioconjugate (PLGA-HSP-TF NPs) exploration in vitro vivo antineoplastic potential. PLGA nanoparticles (NPs), PLGA-HSP NPs, PLGA-HSP-TF NPs were synthesized characterized by DLS, FTIR, FE-SEM, 1H NMR spectroscopy. stability release profile inspected, efficacy was scrutinized terms cytotoxicity, oxidative stress apoptosis biomarkers, cell cycle arrest. In tumor regression host survival studies executed Ehrlich ascites carcinoma (EAC) cell-bearing Swiss albino mice. drug uptake highly stable accomplished effectively MDA-MB-231 cells showed pH-dependent intracellular HSP, which generated excessive reactive oxygen species (ROS) that led assault TNBC cells. This elevated ROS dropped mitochondrial membrane potential triggered apoptosis-mediated death arresting at G0/G1 phase. Furthermore, unveiled significant compared free HSP with minimum toxicity dose 20 mg/kg body weight. divulges may be an astounding nanocandidate for triple-negative therapy.

Язык: Английский

Процитировано

3
Fibroblast Growth Factor Receptor 4 Promotes Triple‐Negative Breast Cancer Progression via Regulating Fatty Acid Metabolism Through the AKT/RYR2 Signaling DOI Creative Commons

Jinhui Ye,

Song Wu,

Qiang Quan

и другие.

Cancer Medicine, Год журнала: 2024, Номер 13(23)

Опубликована: Дек. 1, 2024

Triple-negative breast cancer (TNBC) is the most aggressive subtype of cancer. Previous studies have found that fibroblast growth factor receptor 4 (FGFR4) plays a crucial role in tumor development and metastasis. However, potential underlying mechanisms FGFR4 progression TNBC remain unclear.

Язык: Английский

Процитировано

3
Tetrahydrocurcumin targets TRIP13 inhibiting the interaction of TRIP13/USP7/c-FLIP to mediate c-FLIP ubiquitination in triple-negative breast cancer DOI Creative Commons
Yujie Sun, Qiang Zhang, Shijie Cao

и другие.

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 1, 2024

Triple-negative breast cancer (TNBC) has a high mortality rate and limited treatment options. Tetrahydrocurcumin (THC), major metabolite of curcumin, potential antitumor activities. However, the effects mechanism THC in TNBC remain elusive.

Язык: Английский

Процитировано

2
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

Процитировано

2