ELF1-activated FOXD3-AS1 promotes the migration, invasion and EMT of osteosarcoma cells via sponging miR-296-5p to upregulate ZCCHC3

Osteosarcoma (OS) is a malignant carcinoma often occurring in adolescents. The critical function of long non-coding RNAs (lncRNAs) in cancer arouses increasing attention. Nevertheless, the specific function of FOXD3 Antisense RNA 1 (FOXD3-AS1) in OS has not been understood yet. In this research, FOXD3-AS1 showed strengthened level in OS specimens and cell lines, and its deficiency restrained cell migration, invasion and epithelial-to-mesenchymal transition (EMT) in OS. Then, we confirmed the interaction of FOXD3-AS1 with microRNA-296-5p (miR-296-5p) and that miR-296-5p overexpression blocked OS cell migration, invasion and EMT. Besides, miR-296-5p targeted zinc finger CCHC-type containing 3 (ZCCHC3), and FOXD3-AS1 released ZCCHC3 via sequestering miR-296-5p. Moreover, rescue assays delineated that ZCCHC3 upregulation neutralized the inhibitory effect of FOXD3-AS1 depletion on in vitro behaviors and in vivo tumorigenesis in OS. In addition, E74 like ETS transcription factor 1 (ELF1) stimulated FOXD3-AS1 transcription, and ELF1 silence-suppressed malignant phenotypes of OS cells were offset by FOXD3-AS1 upregulation. Overall, present work elucidated that ELF1-activated FOXD3-AS1 aggravated cell migration, invasion and EMT in OS via absorbing miR-296-5p to augment ZCCHC3 expression, which might provide potential guidance for researchers to find effective targets for OS treatment.