RESUMEN
BACKGROUND: The micro RNA (miRNA)/histone deacetylase 9 (HDAC9) signaling axis has been reported to be involved in initiating and developing multiple malignant tumors. In the present study, we aimed to determine whether miR-211-5p serves as a post-transcriptional regulator in bladder cancer (BCa) cell proliferation and apoptosis by targeting HDAC9. METHODS: miRNA expression profiling of BCa tissues and para-carcinoma tissues was screened by miRNA microarray. After transfection with miR-211-5p mimics or short hairpin RNA of HDAC9 (sh-HDAC9), mRNA and protein expression was evaluated using a quantitative reverse transcription-polymerase chain reaction and western blotting, respectively. A bioinformatics algorithm was used, and a dual-luciferase reporter assay was performed to validate HDAC9 as a direct target of miR-211-5p. Cell proliferation was analyzed by the 3-(4, 5-dimethylthiazl2-yl)-2,5-diphenyltetazolium bromide (MTT) assay. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) detection was used to evaluate apoptosis in 5637 and T24 cells. A transwell assay was used to assess migration and invasion. RESULTS: miR-211-5p is down-regulated in BCa tumor tissues and cell lines. miR-211-5p is identified as an independent biomarker for predicting overall survival. HDAC9 is a direct target of miR-211-5p, and overexpression of miR-211-5p represses HDAC9 protein expression in vitro. Overexpression of miR-211-5p or HDAC9 knockdown significantly inhibits proliferation, migration and invasion of 5637 and T24 cells, and also induces cell apoptosis. CONCLUSIONS: miR-211-5p may play a role as a tumor suppressor and as a favourable prognostic marker in BCa.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Histona Desacetilasas/metabolismo , MicroARNs/genética , Proteínas Represoras/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Femenino , Histona Desacetilasas/genética , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Represoras/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
AIMS: The purpose of this paper is to unearth the ceRNA regulatory mechanism of SNHG7 in bladder cancer (BCa). MATERIALS AND METHODS: The expression of SNHG7 in BCa cells was uncovered by qRT-PCR. The biological functions of SNHG7 in BCa cells were explored by CCK-8 assay, colony formation assay, flow cytometry analysis, wound healing assay and transwell assay. Luciferase reporter assay and RIP assay were applied to analyze the interaction of ELK1 with SNHG7 or miR-2682-5p. KEY FINDINGS: SNHG7 was conspicuously highly expressed in BCa tissues and cells. The upregulated expression of SNHG7 was related with poor prognosis in BCa patients. Moreover, SNHG7 exerted oncogenic functions in BCa through enhancing cell growth, migration and invasion. ELK1 increased the level of SNHG7 by binding with the promoter region of SNHG7. SNHG7 strengthened the expression of ELK1 via acting as a sponge of miR-2682-5p. Both ELK1 and miR-2682-5p involved in the SNHG7-mediated BCa progression. SIGNIFICANCE: ELK1/SNHG7/miR-2682-5p feedback loop enhances cell growth, migration and invasion in BCa.
Asunto(s)
MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias de la Vejiga Urinaria/patología , Proteína Elk-1 con Dominio ets/genética , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Progresión de la Enfermedad , Retroalimentación Fisiológica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones , Ratones Desnudos , Pronóstico , Regulación hacia Arriba , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The elevated expressions of RNA-binding protein HuR and long noncoding HOX transcript antisense RNA (HOTAIR) are observed in numerous cancers. And HuR often exerts its promotive effects on tumorigenesis via binding to AU-rich elements in target transcripts and thus regulating the expression of target transcripts. However, the roles and related mechanisms of HuR/HOTAIR in bladder cancer progression have never been formally tested. Here, we found that the expression level of HuR was higher in clinical bladder cancer samples than in normal adjacent samples, mirroring that of HOTAIR, and their expression showed strong correlation. Knockdown of HuR/HOTAIR in bladder cancer inhibited cell proliferation, migration, invasion, and promoted cell apoptosis. Notably, HuR interacted and stabilized HOTAIR mRNA and knockdown of HuR decreased HOTAIR expression. Additionally, HOTAIR was identified as a potential target of miR-1 in bladder cancer cells. Interestingly, overexpression of HOTAIR enhanced HuR expression and increased cytoplasmic accumulation of HuR, thus enhancing HOTAIR expression in turn. But mutation of miR-1 binding site in HOTAIR canceled the effects of HOTAIR on HuR expression. Overall, we identified a regulatory loop between HOTAIR and HuR during the progression of bladder cancer, which could be exploited to curb bladder cancer progression.