RESUMO
Recent studies have shown that long non-coding RNAs (lncRNAs) have critical roles in tumorigenesis, including osteosarcoma. The lncRNA taurine-upregulated gene 1 (TUG1) was reported to be involved in the progression of osteosarcoma. Here, we investigated the role of TUG1 in osteosarcoma cells and the underlying mechanism. TUG1 expression was measured in osteosarcoma cell lines and human normal osteoblast cells by quantitative real-time PCR (qRT-PCR). The effects of TUG1 on osteosarcoma cells were studied by RNA interference in vitro and in vivo. The mechanism of competing endogenous RNA (ceRNA) was determined using bioinformatic analysis and luciferase assays. Our data showed that TUG1 knockdown inhibited cell proliferation and colony formation, and induced G0/G1 cell cycle arrest and apoptosis in vitro, and suppressed tumor growth in vivo. Besides, we found that TUG1 acted as an endogenous sponge to directly bind to miR-9-5p and downregulated miR-9-5p expression. Moreover, TUG1 overturned the effect of miR-9-5p on the proliferation, colony formation, cell cycle arrest, and apoptosis in osteosarcoma cells, which involved the derepression of POU class 2 homeobox 1 (POU2F1) expression. In conclusion, our study elucidated a novel TUG1/miR-9-5p/POU2F1 pathway, in which TUG1 acted as a ceRNA by sponging miR-9-5p, leading to downregulation of POU2F1 and facilitating the tumorigenesis of osteosarcoma. These findings may contribute to the lncRNA-targeted therapy for human osteosarcoma.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias Ósseas/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Fator 1 de Transcrição de Octâmero/metabolismo , Osteossarcoma/patologia , RNA Longo não Codificante/genética , Apoptose , Western Blotting , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Ciclo Celular , Proliferação de Células , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Citometria de Fluxo , Humanos , Fator 1 de Transcrição de Octâmero/genética , Osteossarcoma/genética , Osteossarcoma/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais CultivadasRESUMO
PURPOSE: Functional MR imaging of the human cervical spinal cord was carried out on volunteers during alternated rest and a complex finger tapping task, in order to detect image intensity changes arising from neuronal activity. METHODS: Functional MR imaging data using single-shot fast spin-echo sequence (SSFSE) with echo time 42.4 ms on a 1.5 T GE Clinical System were acquired in eight subjects performing a complex finger tapping task. Cervical spinal cord activation was measured both in the sagittal and transverse imaging planes. Postprocessing was performed by AFNI (Analysis of Functional Neuroimages) software system. RESULTS: Intensity changes (5.5-7.6%) were correlated with the time course of stimulation and were consistently detected in both sagittal and transverse imaging planes of the cervical spinal cord. The activated regions localized to the ipsilateral side of the spinal cord in agreement with the neural anatomy. CONCLUSION: Functional MR imaging signals can be reliably detected with finger tapping activity in the human cervical spinal cord using a SSFSE sequence with 42.4 ms echo time. The anatomic location of neural activity correlates with the muscles used in the finger tapping task.
Assuntos
Vértebras Cervicais/fisiologia , Potencial Evocado Motor/fisiologia , Dedos/fisiologia , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Movimento/fisiologia , Medula Espinal/fisiologia , Adulto , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Sensibilidade e EspecificidadeRESUMO
PURPOSE: Functional MR imaging of the human cervical spinal cord was carried out on volunteers by 20Hz functional electrical stimulation to median nerve, in order to detect signal changes arising concomitant to neuronal activity. METHODS: Functional MR imaging data were acquired in six subjects with single-shot fast spin-echo sequence (SSFSE) on a 1.5T GE Clinical System. Cervical spinal cord activation was measured both in the sagittal and transverse imaging planes. Postprocessing was performed by AFNI (Analysis of Functional Neuroimages) software system. RESULTS: Activation correlated with the time course of stimulation was consistently detected in both sagittal and transverse imaging planes of the cervical spinal cord. Regions of the spinal cord associated with motor and pain response were observed by 20Hz functional electrical stimulation to the median nerve. CONCLUSION: The functional MR imaging signal can be detected in the human cervical spinal cord with functional electrical stimulation. Investigating the FES response in the spinal cord using the spinal fMRI will be helpful for the further discussion on the diagnosis and functional recovery to spinal cord diseases.