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 is a malignant tumor in children and adolescents. Previous studies showed that ATG4A is an autophagy-related gene involved in cancers. In this study, we aimed to identify the biological role of ATG4A in osteosarcoma. The expression levels of ATG4A were analyzed in osteosarcoma tissues by using reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and western blotting. ATG4A was knocked-down or overexpressed in SAOS2 and HOS cell lines by transfection. Cell counting kit-8 (CCK-8) and clone formation assay were used to assess the effects of ATG4A on cell proliferation. Wound healing and Transwell assays were performed to evaluate the effects of ATG4A on cell migration and invasion, respectively. Epithelial-mesenchymal transition (EMT) markers and Notch signaling pathway targeting molecules were examined by western blotting. The results indicated that ATG4A was up-regulated in osteosarcoma tissues. In SAOS2 cells, knockdown of ATG4A inhibited the proliferation, migration and invasion, up-regulated the expression of E-cadherin and down-regulated the expression of vimentin, Notch1 and Hes1. In HOS cells, overexpression of ATG4A promoted the proliferation, migration and invasion, up-regulated the expression of vimentin, Notch1 and Hes1 and down-regulated the expression of E-cadherin. In conclusion, these findings demonstrate that ATG4A is up-regulated in osteosarcoma tissues. In osteosarcoma cells, ATG4A promotes the EMT process partly by the Notch signaling pathway. These results suggest that ATG4A might represent a potential therapeutic target for patients with osteosarcoma.
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PMID:Upregulation of ATG4A promotes osteosarcoma cell epithelial-to-mesenchymal transition through the Notch signaling pathway. 3196 49

Doxorubicin (Dox) is one of the most commonly used chemotherapeutic drugs for osteosarcoma (OS) treatment. In the present study, we attempted to investigate the mechanism by which Sox2OT-V7 dysregulation affects Dox chemoresistance to provide a novel experimental basis for developing neoadjuvant therapy. Sox2OT-V7 expression is upregulated in OS tissues, particularly in chemoresistant OS tissues, and in OS cell lines compared to controls. Dox treatment induces autophagy and Sox2OT-V7 expression in U2OS cells, and Dox-induced autophagy is partially attenuated by Sox2OT-V7 silencing. Knocking down Sox2OT-V7 or blocking autophagy in Dox-resistant U2OS/Dox cells resensitizes the cells to Dox treatment in vitro. Moreover, Sox2OT-V7 directly targets miR-142/miR-22 to inhibit their expression, and the effect of Sox2OT-V7 silencing on U2OS cell autophagy and U2OS/Dox cell sensitivity to Dox can be reversed by miR-142/miR-22 inhibition. Sox2OT-V7 silencing enhances the suppressive effects of Dox on U2OS/Dox cell-derived tumor growth in vivo, while miR-22 inhibition or miR-142 inhibition reverses the effects of Sox2OT-V7 silencing on Dox-induced suppression on tumor growth. Finally, miR-142 directly targets ULK1, ATG4A, and ATG5, while miR-22 directly targets ULK1 to inhibit the expression of the target gene; The Sox2OT-V7/miR-142/miR-22 axis modulates autophagy in OS cells by regulating ULK1, ATG4A, and ATG5.
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PMID:LncRNA Sox2OT-V7 promotes doxorubicin-induced autophagy and chemoresistance in osteosarcoma via tumor-suppressive miR-142/miR-22. 3230 91