title: Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma.
abstract: In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear.
  
  
  
  The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b.
  
  
  
  MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits.
  
  
  
  These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Xing
authors: X
authors: Bao
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Tingting
authors: T
authors: Ren
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Yi
authors: Y
authors: Huang
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Shidong
authors: S
authors: Wang
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Fan
authors: F
authors: Zhang
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Kuisheng
authors: K
authors: Liu
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China.
authors: Bingxin
authors: B
authors: Zheng
authors: Musculoskeletal Tumor Center, Peking University People's Hospital, No.11 Xizhimen South Street, Beijing, 100044, People's Republic of China. bonetumor@163.com.|Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, 100044, People's Republic of China. bonetumor@163.com.
authors: Wei
authors: W
authors: Guo
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000235:genetics; D000073399:DNA Demethylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010087:Oxides / Q000008:administration & dosage* / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D001152:Arsenicals; C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D010087:Oxides; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077237:Arsenic Trioxide
keywords: Arsenic trioxide (ATO); Chondrosarcoma; Metastatsis; MicroRNA-125b; Signal transducer and activator of transcription3(Stat3)