RESUMEN
BACKGROUND: Breast cancer is one of the most common tumors for women globally. Various miRNAs have been reported to play a crucial role in breast cancer, however the clinical significance of miR-1908-3p in breast cancer remains unclear. The present study aimed to explore the role of miR-1908-3p in breast cancer. METHODS: The expression of miR-1908-3p was detected in 50 pairs of breast cancer tissues and adjacent normal tissues, 60 breast cancer patient serum and 60 healthy volunteer serum. The functional roles of miR-1908-3p in breast cancer cells such as proliferation, migration and invasion were evaluated using CCK8, SRB, wound healing and transwell chambers. In addition, bioinformatics tools were used to identify potential targets of miR-1908-3p. RESULTS: The results showed that the expression of miR-1908-3p were increased in breast cancer tissues and serum compared with normal breast tissues and serum of healthy volunteers respectively. Furthermore, the young breast cancer patients and HER2-positive patients had a higher level of tissues' miR-1908-3p than elder breast cancer patients and HER2-negative patients, respectively. The young breast cancer patients had a higher level of serum miR-1908-3p than elder breast cancer patients, ROC analysis suggested that miR-1908-3p had the potential as a promising serum diagnostic biomarker of breast cancer. Up-regulation of miR-1908-3p promoted the cells proliferation, migration and invasion while knockdown of miR-1908-3p inhibited these processes in breast cancer cell MCF-7 and MDA-MB-231. The potential target genes of miR-1908-3p in breast cancer included ID4, LTBP4, GPM6B, RGMA, EFCAB1, ALX4, OSR1 and PPARA. Higher expression of these eight genes correlated with a better prognosis for breast cancer patients. CONCLUSIONS: These results suggest that miR-1908-3p may exert its oncogenic functions via suppression of these eight genes in breast cancer.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Carcinogénesis/patología , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinogénesis/genética , Carcinogénesis/metabolismo , Estudios de Casos y Controles , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Células Tumorales CultivadasRESUMEN
BACKGROUND: Eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Changes in eIF4E activity disproportionally affect the translation of a subset of oncogenic mRNAs in some cancers. MATERIALS AND METHODS: We have assessed the expression levels of vascular endothelial growth factor C (VEGFC), eIF4E, eIF4E-binding proteins (4E-BPs) and phospho-4E-BP1 in clear cell renal carcinoma (ccRCC; n=101) using immunohistochemistry and analyzed the relevant mRNA levels and survival using online databases. RESULTS: The protein levels of VEGFC, an eIF4E-regulated gene, were upregulated in ccRCC tissues compared with adjacent normal renal tissues, indicating an enhanced eIF4E activity in ccRCC. The expression of eIF4E had no significant changes in ccRCC tissues. However, 4E-BP1 and phospho-4E-BP1 were found to be overexpressed in ccRCC tissues (P<0.05), and the high mRNA and protein levels of 4E-BP1 and phospho-4E-BP1 correlated with an unfavorable clinical outcome in ccRCC patients. Meanwhile, the mRNA expression of PIK3CD and PIK3CG were enhanced in ccRCC. CONCLUSION: From these results, we could infer that the increase in eIF4E activity may be caused by the increased phospho-4E-BP1 level, which was probably due to the activation of phosphoinositide 3-kinase (PI3K) pathway.