RESUMEN
Recent data strongly suggest the important role of miRNAs in various cancer-related processes. Osteosarcoma (OS) is the most common primary cancer of the bone and usually leads to deaths due to its rapid proliferation and metastasis. Here, we demonstrated that compared with noncancerous bone tissues, miR-135b expression is frequently upregulated in OS specimens, inversely correlated with potential target-FOXO1 expression pattern. Bioinformatics analysis combined with experimental confirmation revealed FOXO1 is a direct target of miR-135b in OS. Functionally, miR-135b inhibitor significantly inhibited OS cells proliferation and invasion. Forced expression of FOXO1 showed the opposite effect, and FOXO1 knockdown abolished the effect of miR-135b inhibitor. Taken together, our data provide compelling evidence that miR-135b functions as an onco-miRNA in OS to promote OS cells proliferation and invasion, and its oncogenic effects are mediated chiefly through targeting FOXO1.
Asunto(s)
Factores de Transcripción Forkhead/genética , MicroARNs/biosíntesis , Osteosarcoma/genética , Línea Celular Tumoral , Proliferación Celular/genética , Proteína Forkhead Box O1 , Factores de Transcripción Forkhead/biosíntesis , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Invasividad Neoplásica/genética , Osteosarcoma/patologíaRESUMEN
OBJECTIVE: Recent reports strongly suggest the profound role of miRNAs in cancer therapeutic response and progression, including invasion and metastasis. The sensitivity to therapy and invasion is the major obstacle for successful treatment in prostate cancer. We aimed to investigate the regulative effect of miR-128/zinc-finger E-box-binding homeobox 1 axis on prostate cancer cell chemosensitivity and invasion. METHODS: The miR-128 expression pattern of prostate cancer cell lines and tissues was detected by real-time reverse transcriptase-polymerase chain reaction, while the mRNA and protein expression levels of zinc-finger E-box-binding homeobox 1 were measured by real-time reverse transcriptase-polymerase chain reaction and western blot assay, respectively. Dual-luciferase reporter gene assay was used to find the direct target of miR-128. Furthermore, prostate cancer cells were treated with miR-128 mimic or zinc-finger E-box-binding homeobox 1-siRNA, and then the cells' chemosensitivity and invasion were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and transwell assay, respectively. RESULTS: We found miR-128 expression obviously decreased in prostate cancer tissues compared with paired normal tissues. Restored miR-128 expression sensitized prostate cancer cells to cisplatin and inhibited the invasion. Furthermore, there was an inverse expression pattern between miR-128 and zinc-finger E-box-binding homeobox 1 in prostate cancer cells and tissues, and zinc-finger E-box-binding homeobox 1 was identified as a direct target of miR-128 in prostate cancer. Knockdown of zinc-finger E-box-binding homeobox 1 expression efficiently sensitized prostate cancer cells to cisplatin and inhibited the invasion. However, ectopic zinc-finger E-box-binding homeobox 1 expression impaired the effects of miR-128 on chemosensitivity and invasion in prostate cancer cells. CONCLUSIONS: miR-128 functions as a potential cancer suppressor in prostate cancer progression and rational therapeutic strategies for prostate cancer would be developed based on miR-128/zinc-finger E-box-binding homeobox 1 axis.