FOXO1-MALAT1-miR-26a-5p Feedback Loop Mediates Proliferation and Migration in Osteosarcoma Cells.
miR-26a has been found to be downregulated in osteosarcoma (OS) when compared with normal control tissues and has been shown to suppress the malignant behaviors of OS cells. The underlying mechanism, nevertheless, remains unknown. In our study, the long noncoding RNA MALAT1, confirmed to be significantly upregulated in OS, is first shown to be capable of promoting proliferation and migration by directly suppressing miR-26a-5p in OS cells. In addition, we have identified forkhead box O1 (FOXO1) as a transcriptional factor of MALAT1 that can negatively regulate MALAT1. We have shown that MALAT1 promoted growth and migration through inhibiting miR-26a-5p in OS cells. Suppression of FOXO1, identified as a regulatory transcriptional factor of MALAT1, was shown to be able to slow down both proliferation and metastases in OS cells, suggesting that targeting FOXO1 can be useful in the therapy of patients with OS.
Juntao
J
Wang
Guodong
G
Sun
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D025461:Feedback, Physiological; D005260:Female; D000071161:Forkhead Box Protein O1 / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D000071161:Forkhead Box Protein O1; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C085126:FOXO1 protein, human; C557041:MALAT1 long non-coding RNA, human; C528163:MIRN26 microRNA, human