ABSTRACT
Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.
ABSTRACT
Studies have proved that microRNA-101 (miR-101) functions as a tumor suppressor and is associated with growth and apoptosis of various human cancers. However, the role of miR-101 in osteosarcoma and the possible mechanism by which miR-101 affects the tumor growth and apoptosis have not been fully elucidated. In this study, we found that the expression of miR-101 was down-regulated in osteosarcoma tissues and Saos-2 cell line as compared with that in adjacent non-neoplastic bone tissues and the osteoblastic cell line. To better characterize the role of miR-101 in osteosarcoma, we used a gain-of-function analysis by transfecting human osteosarcoma cell line Saos-2 with chemically synthesized miR-101 mimics. The results showed that overexpression of miR-101 inhibited the proliferation and promoted the apoptosis of Saos-2 cells. Meanwhile, bioinformatic analysis demonstrated that mTOR gene was a direct target of miR-101. Overexpression of miR-101 significantly decreased the expression of mTOR at both mRNA and protein levels in Saos-2 cells, consequently inhibiting Saos-2 cells proliferation and promoting cells apoptosis in an mTOR-dependent manner. Taken together, these data suggest that miR-101 may act as a tumor suppressor, which is commonly downregulated in both osteosarcoma tissues and cells. mTOR plays an important role in mediating miR-101 dependent biological functions in osteosarcoma. Reintroduction of miR-101 may be a novel therapeutic strategy by down-regulating mTOR expression.
Subject(s)
Humans , Apoptosis , Bone Neoplasms , Genetics , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , MicroRNAs , Genetics , Metabolism , Neoplasm Proteins , Genetics , Metabolism , Osteosarcoma , Genetics , Metabolism , Pathology , RNA, Neoplasm , Genetics , Metabolism , TOR Serine-Threonine Kinases , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To assess the diagnostic value of magnetic resonance imaging (MRI) in the follow-up of patients with hepatocellular carcinomas treated with radiofrequency ablation (RFA) and to compare it with that of computed tomography (CT).</p><p><b>METHODS</b>From December 2009 to September 2011, 40 patients (47 hepatocellular carcinomas) were treated with RFA after transcatheter arterial chemoembolization and underwent MRI and CT for follow-up. RFA margins were assessed on a five-point scale with receiver operating characteristic curve analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were evaluated.</p><p><b>RESULTS</b>The interobserver agreement rate for MRI was significantly higher (Kappa=0.935) than for CT (Kappa=0.714; P < 0.05). The scores of 1 and 5 points for MRI, which confirms the presence or absence of residual tumor, accounted for 89.4% (84/94), while for CT accounting for only 31.9% (30/94). The area under the receiver operating characteristic curve of MRI was significantly higher than that of CT (P < 0.05), as were the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of detection rate (mean, 100%, 96.4%, 76.9%, 100%, and 96.8% for MRI, respectively, vs. 30.0%, 57.1%, 10.3%, 87.7%, and 63.8% for CT).</p><p><b>CONCLUSION</b>MRI is superior to CT in assessing the RFA margins in terms of the diagnostic accuracy and detection rate .</p>