RESUMEN
BACKGROUND: Breast cancer is the leading cause of cancer deaths in women worldwide. The purpose of the current study was to investigate the potential role of miR-96-5p in breast cancer. METHODS: Breast cancer tissues and matched para-cancerous tissues were collected. The expression of microRNA-96-5p (miR-96-5p) and arginine kinase 3 (AK3) was detected by quantitative real-time PCR (qRT-PCR). The correlation between miR-96-5p and AK3 was calculated by Pearson's Chi-square test. Moreover, mimics or inhibitors of miR-96-5p were applied to explore whether miR-96-5p influences the migration capacity in Transwell and wound healing assays. Bioinformatics analysis was performed to identify the target genes of miR-96-5p through the TargetScan, miRDB and miRanda databases. A luciferase reporter assay was performed to verify AK3 as a downstream target gene of miR-96-5p. RESULTS: The expression of miR-96-5p was significantly increased in breast cancer tissue and breast cancer cell lines compared with para-cancerous tissue and a breast cell line, respectively. The expression of miR-96-5p negatively correlated with AK3 gene expression. AK3 was demonstrated to be a direct mRNA target of miR-96-5p. AK3 was positively associated with the overall survival of breast cancer patients. Kaplan-Meier curve and log rank test analyses revealed that decreased AK3 levels were significantly associated with reduced overall survival. miR-96-5p was shown to promote the migration of breast cancer cells through the MEK/ERK signaling pathway. CONCLUSION: Our results identify a role for miR-96-5p in promoting breast cancer cell migration through activation of MEK/ERK signaling by targeting AK3.
Asunto(s)
Arginina Quinasa/metabolismo , Neoplasias de la Mama/patología , MicroARNs/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Arginina Quinasa/genética , Neoplasias de la Mama/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , MicroARNs/genética , Quinasas de Proteína Quinasa Activadas por Mitógenos/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Transducción de SeñalRESUMEN
In the title compound, C(10)H(10)N(2)O(2), all non-H atoms are approximately co-planar with an r.m.s. deviation of 0.016â Å. In the crystal, mol-ecules are linked into inversion dimers by pairs of N-Hâ¯O hydrogen bonds. Chains along [010] are buiilt up by π-π inter-actions [centroid-centroid distance = 3.602â (1)â Å] between the benzene and piperazine rings of adjacent mol-ecules.
RESUMEN
The title compound, C(11)H(12)N(2)O(2), shows an S configuration, in which the pyrrolidinone ring is twisted with respect to the phenyl plane, making a dihedral angle of 70.73â (7)°. In the crystal, mol-ecules are linked by N-Hâ¯O hydrogen bonds, building up a layer parallel to (001).