Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Osteosarcoma (OS) is a prevalent cancer that plagues people worldwide. Identifying prognostic markers would be useful in treating human OS. In this study, we aimed to explore the functions of Ras-related protein Rab-31 (RAB31) in OS-cell proliferation, migration, and invasion as well as its roles in the Hedgehog signaling pathway for better understanding of the mechanism. To assess the detailed regulatory mechanism of RAB31 silencing on OS, both RT-qPCR and Western blot analysis were employed to evaluate the expressions of RAB31 as well as the Hedgehog signaling pathway-related genes. Besides, we also investigated the effects of silenced RAB31 both in vitro and in vivo. First, we found that in OS tissues, both mRNA and protein expressions of RAB31 and PCNA had a significant increase. Second, the Hedgehog signaling pathway was detected to play an integral role in OS progression. Finally, after transfection of RAB31-siRNA to reduce the expression of RAB31, the Hedgehog signaling pathway was suppressed, along with cell proliferation, invasion, and migration. Therefore, we conclude that RAB31 plays an important role in OS development and its silencing delays the OS progression via suppression of the Hedgehog signaling pathway.
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PMID:Effect of RAB31 silencing on osteosarcoma cell proliferation and migration through the Hedgehog signaling pathway. 3251 35

Osteosarcoma (OS) is a rare malignancy of bone associated with poor clinical outcomes. The antitumor effects of GANT61 on OS is unclear. To investigate antitumor effects and mechanism of GANT61 in OS cells and xenograft model. Effects of GANT61 on cell viability, clone formation, cell cycle, apoptosis, migration, and invasion ability of OS cells were assessed. Reactive oxygen species (ROS) levels measured by dichlorofluorescein fluorescence were used to evaluate oxidative stress. The Xenograft model was constructed to investigate the antitumor effects of GANT61 in vivo. The microRNA (miRNA)-1286 was downregulated, while RAB31 upregulated in OS tissues and cells. GANT61 inhibited viability, migration, and invasion ability of OS cells (SaOS-2 and U2OS), and induced apoptosis and the ROS production, along with miRNA-1286 upregulation and RAB13 downregulation. After knockdown of miRNA-1286, GANT6-induced cell inhibition was attenuated, along with RAB31 upregulation. Inversely, miRNA-1286 overexpression downregulated RAB31. Dual-luciferase reporter assay verified that miR-1286 negatively targeted RAB13. Moreover, the knockdown of RAB31 stimulated apoptosis and ROS production while inhibited viability, migration, and invasion of GANT61-treated cells. In vivo experiments further confirmed that GANT61 inhibited tumor growth and RAB13 expression, but enhanced miRNA-1286. The study demonstrated that GANT61 inhibited cell aggressive phenotype and tumor growth by inducing oxidative stress through the miRNA-1286/RAB31 axis. Our findings provided a potential antitumor agent for the OS clinical treatment.
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PMID:GANT61 plays antitumor effects by inducing oxidative stress through the miRNA-1286/RAB31 axis in osteosarcoma. 3293 98

Ras-related protein Rab-31 (RAB31), a small guanosine 5'-triphosphate-binding protein, is a member of the Rab family and has been demonstrated to serve an oncogenic role in several common types of human cancer. However, the function of RAB31 in osteosarcoma (OS) has not been previously studied. The present study identified that the expression levels of RAB31 were significantly higher in OS tissue samples compared with matched adjacent non-tumor tissue samples, and high RAB31 expression was associated with malignant progression and a poor prognosis for patients with OS. Furthermore, it was identified that the expression levels of RAB31 were increased in OS cell lines compared with normal osteoblast cells. Silencing of RAB31 expression significantly inhibited OS cell proliferation, cell cycle progression, migration and invasion, and significantly increased the rate of cell apoptosis. In addition, the present study used a luciferase reporter assay to demonstrate that RAB31 was a direct target gene of microRNA-26b (miR-26b), which is a known tumor suppressor in OS. The expression levels of RAB31 were negatively associated with miR-26b expression in OS cells. Finally, miR-26b was demonstrated to be significantly decreased in OS tissues compared with adjacent non-tumor tissues, and an inverse correlation was observed between the expression levels of RAB31 and miR-26b in OS tissues. In summary, to the best of our knowledge, the present study is the first to report that RAB31 is a target gene of miR-26b, and silencing of RAB31 may inhibit OS growth and progression.
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PMID:RAB31 is targeted by miR-26b and serves a role in the promotion of osteosarcoma. 3297 57