RESUMEN
The upregulation of methyltransferase-like 3 (METTL3) has been associated with the progression of esophageal cancer. However, METTL3-induced N6-methyladenosine (m6A) alterations on the downstream target mRNAs in esophageal squamous cell carcinoma (ESCC) are not yet fully understood. Our study revealed that silencing METTL3 resulted in a significant decrease in ESCC cell proliferation and metastasis in vitro and in vivo. Additionally, the adhesion molecule with Ig like domain 2 (AMIGO2) was identified as a potential downstream target of both METTL3 and YTH Domain-Containing Protein 1 (YTHDC1) in ESCC cells. Functionally, AMIGO2 augmented the malignant behaviors of ESCC cells in vitro and in vivo, and its overexpression can rescue the inhibition of the proliferation and migration in ESCC cells induced by METTL3 or YTHDC1 knockdown. Furthermore, our findings revealed that knockdown of METTL3 decreased m6A modification in the 5'-untranslated regions (5'UTR) of AMIGO2 precursor mRNA (pre-mRNA), and YTHDC1 interacted with AMIGO2 pre-mRNA to regulate AMIGO2 expression by modulating the splicing process of AMIGO2 pre-mRNA in ESCC cells. These findings highlighted a novel role of the METTL3-m6A-YTHDC1-AMIGO2 axis in regulating ESCC cell proliferation and motility, suggesting its potential as a therapeutic target for ESCC.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/patología , Precursores del ARN/metabolismo , Proliferación Celular/genética , Regulación hacia Arriba , Metiltransferasas/genética , Metiltransferasas/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Factores de Empalme de ARN/genéticaRESUMEN
Ribosome biogenesis is a cellular process critical for protein homeostasis during cell growth and multiplication. Our previous study confirmed up-regulation of ribosome biogenesis during endometriosis progression and malignant transition, thus anti-ribosome biogenesis may be effective for treating endometriosis and the associated complications. A mouse model with human endometriosis features was established and treated with three different drugs that can block ribosome biogenesis, including inhibitors against mTOR/PI3K (GSK2126458) and RNA polymerase I (CX5461 and BMH21). The average lesion numbers and disease frequencies were significantly reduced in treated mice as compared to controls treated with vehicle. Flow cytometry analyses confirmed the reduction of small peritoneal macrophage and neutrophil populations with increased large versus small macrophage ratios, suggesting inflammation suppression by drug treatments. Lesions in treated mice also showed lower nerve fiber density which can support the finding of pain-relief by behavioral studies. Our study therefore suggested ribosome biogenesis as a potential therapeutic target for treating endometriosis.
RESUMEN
Bioassay-guided isolation of the aerial part of Scutellaria barbata yielded three new neo-clerodane diterpenoids scutebatas P-R (1-3), together with two known ones: scutebata E (4) and scutebarbatine B (5). The chemical structures of the isolated compounds were elucidated by spectroscopic methods (NMR and MS) and by comparison with the spectroscopic data reported in the literature. All compounds except 3 showed weak cytotoxicity with IC50 values ranging from 35.11 to 42.73 µM against K562 cell lines, and compounds 1, 2, and 5 also displayed weak activities against HL60 cell lines.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Diterpenos de Tipo Clerodano/aislamiento & purificación , Scutellaria/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Diterpenos de Tipo Clerodano/química , Diterpenos de Tipo Clerodano/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Humanos , Estructura MolecularRESUMEN
AIM: To test the effect of Ginkgo biloba leaf extract on electroencephalography (EEG) during cerebral ischemia and reperfusion. METHODS: Based on the quantitative analysis of EEG using the fast Fourier transform (FFT), the effect of Ginkgo biloba extract (GbE) on rat EEG was surveyed in the model of middle cerebral artery (MCA) occlusion and global cerebral ischemia. RESULTS: In the global cerebral ischemia, GbE 8 and 16 mg/kg could accelerate the recovery of EEG after reperfusion, and GbE 4 mg/kg had the same effect but much weaker. In the MCA occlusion model, GbE 16 and 32 mg/kg greatly suppressed the drop of power spectrum of EEG. CONCLUSION: GbE could mitigate the cerebral damage caused by ischemia.