RESUMEN
The long noncoding (lnc)RNA named tissue differentiation inducing nonprotein coding RNA (TINCR) is a tumor marker that has not been studied in breast cancer. The present study aimed to investigate the TINCRtargeting micro (mi)RNAs and the regulatory mechanisms of TINCR in breast cancer. Following prediction by TargetScan and confirmation by dualluciferase reporter assay, TINCR was demonstrated to be a target gene for miR5893p. The expression of TINCR and miR5893p in breast cancer and adjacent tissues was detected by reverse transcriptionquantitative (RTq)PCR, and the correlation between TINCR and miR5893p expression was determined by using Spearman correlation analysis. The 5years survival was analyzed in patients with breast cancer according to TINCR expression (high or low). The effects of TINCR and miR5893p on the proliferation, apoptosis, migratory and invasive abilities of some breast cancer cell lines were detected by MTT assay, flow cytometry, wound healing assay and Transwell assay. The target gene of miR5893p was predicted and verified by TargetScan and dualluciferase reporter assay, and the mechanism of miR5893p involvement in breast cancer cells was explored by overexpression or downregulation of miR5893p in breast cancer cells. RTqPCR and western blotting were used to determine the expression of the insulinlike growth factor 1 receptor (IGF1R)/AKT pathwayrelated genes. The results demonstrated that TINCR expression level was negatively correlated with miR5893p expression level in breast cancer tissues and that patients with high expression of TINCR presented with lower survival rates. In addition, TINCR overexpression in cancer cells inhibited miR5893p expression, and cell transfection with miR5893p mimic partially reversed the effect of TINCR overexpression on the promotion of cancer cell proliferation, migration and invasion, and on the inhibition of cancer cell apoptosis. Furthermore, IGF1R, which is a target gene of miR5893p, increased cancer cell proliferation, migration and invasion and inhibited cancer cell apoptosis; however, these effects were partially reversed by miR5893p mimic. Furthermore, the results demonstrated that miR5893p mimic could downregulate the protein expression of IGF1R and pAKT. In addition, TINCR overexpression downregulated miR5893p expression level. miR5893p partially reversed the effects of TINCR overexpression on cancer cell proliferation, migration and invasion, and inhibited cancer cell apoptosis by inhibiting the IGF1RAkt pathway. The results from the present study demonstrated that TINCR may sponge miR5893p in order to inhibit IGF1RAkt pathway activation in breast cancer cells, promoting therefore cancer cell proliferation, migration and invasion.
Asunto(s)
Neoplasias de la Mama/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Largo no Codificante/genética , Receptor IGF Tipo 1/genética , Transducción de Señal , Apoptosis , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Receptor IGF Tipo 1/metabolismoRESUMEN
Objective: To investigate the clinical efficacy and safety of endoscopic thyroidectomy through the oral vestibular approach and the breast approach. Methods: Retrospective analysis was done on clinical data of 80 patients who received an endoscopic thyroidectomy from April 2018 to March 2019. The research group had endoscopic thyroidectomy through the oral vestibular approach, whereas the control group had endoscopic thyroidectomy through the areola breast approach. Comparison between the two groups including intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, postoperative hospitalization duration, satisfactory esthetic outcomes of incision, central lymph node clearance, skin injury, infection incidence, and complications such as facial hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was recorded. Results: There was no significant difference between the two groups in the amount of intraoperative bleeding, operation time, total postoperative drainage, drainage time, postoperative sustained pain time, recovery feeding time, and postoperative hospitalization time (P > .05). The incidence of complications such as skin injury, infection, wound hematoma, subcutaneous emphysema, abnormal feeling of the neck and chest, and pleural injury was not statistically different between the two groups (P > .05). There was no significant difference in the number of lymph nodes cleaned in the central area between the two groups (P > .05). The overall satisfaction of the patients with the cosmetic effects of the incision (100.00%) was higher than that of the control group (90.00%). Conclusions: The clinical treatment effect and safety in the two groups were similar, but the transoral group had better cosmetic effects.
Asunto(s)
Endoscopía/métodos , Cirugía Endoscópica por Orificios Naturales/métodos , Neoplasias de la Tiroides/cirugía , Tiroidectomía/métodos , Adulto , Pérdida de Sangre Quirúrgica , Drenaje , Ingestión de Alimentos , Endoscopía/efectos adversos , Estética , Femenino , Hematoma/etiología , Humanos , Tiempo de Internación , Escisión del Ganglio Linfático , Persona de Mediana Edad , Boca , Cirugía Endoscópica por Orificios Naturales/efectos adversos , Pezones , Tempo Operativo , Dolor Postoperatorio/etiología , Pleura/lesiones , Recuperación de la Función , Estudios Retrospectivos , Piel/lesiones , Tiroidectomía/efectos adversosRESUMEN
BACKGROUND: The expression of p38 MAPK is high in breast cancer while its subunit p38γ had been rarely reported. We aimed to explain the effect of p38γ in breast cancer from the perspective of metabolomics. METHODS: In this study, we detected the expression of p38γ in 28 breast carcinoma and para-tumor samples. Following MDA-MB-231 cell transfection with p38γ siRNAs and pc-DNA-3.1, cell viability, apoptosis, metastasis were determined through CCK-8, the cytometry analysis, transwell assay and wound healing assay. Finally, gas chromatograph-mass spectrometer (GC-MS) was used for analysis the differential metabolites. RESULTS: The expression of p38γ was significantly up-regulated in breast cancer tissues. The transfection of si-p38γs could inhibit MDA-MB-231 cell propagation, metastasis, and induced cell apoptosis while overexpressed p38γ could promote the cell propagation, metastasis, and inhibit cell apoptosis. A total of 238 metabolites were identified and 72 of them differentially expressed in three groups (all P < 0.05, FDR < 0.05). Then the metabolites were enriched in the metabolism pathway, 85 pathways were included and 27 were significant (all P < 0.05, FDR < 0.05). CONCLUSIONS: p38γ was up-regulated in breast cancer, which exerts a great influence on the cell growth, cell mobility, invasiveness, and apoptosis of MDA-MB-231 cells and also affected the metabolism.
Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Metabolómica , Proteína Quinasa 12 Activada por Mitógenos/metabolismo , Apoptosis , Neoplasias de la Mama/genética , Línea Celular Tumoral , Movimiento Celular , Supervivencia Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Persona de Mediana Edad , Proteína Quinasa 12 Activada por Mitógenos/genética , Invasividad NeoplásicaRESUMEN
p53 is the most highly mutated tumor suppressor in human malignancies. A wide array of p53 mutations has been revealed to play pivotal roles during cancer progression, which abolish anti-tumor functions of wild type p53 but also elicit tumorigenic effects by activating a diverse subset of downstream molecules. R273H mutation of p53 has been closely implicated in human cancer. Here we report miR-30a as a novel downstream target of p53 R273H mutant, which binds to the promoter region to repress miR-30a expression. Consequently, p53 R273H mutant enhances the migratory capabilities of tumor cells that are compromised by exogenous miR-30a over-expression. Our further investigation indicates that p53 R273H mutation unleashes the inhibition effect of miR-30a on IGF-1R expression, thus leading to elevated activation of IGF-1R-AKT signaling cascade in tumor cells.