Osteosarcoma is a bone tumor primary malignancy. Lysyl hydroxylase 2 (LH2, encoded by the PLOD2 gene) is a major enzyme in modification of fibrotic collagen and enhancement of tumor cell metastasis. Apelin (APLN), an adipokine secreted by adipose tissue, is upregulated in different cancers and promotes angiogenesis, metastasis and cell proliferation, but its effects on osteosarcoma cell migration are uncertain. We therefore determined the function of APLN in the migration of human osteosarcoma cell lines 143B and MG63. Our finding showed that APLN expression levels in osteosarcoma tissue are higher than that in normal tissue. This study found that APLN induces osteosarcoma cell migration by promoting PLOD2 expression. Our investigations indicated that APLN enhances PLOD2 expression and the osteosarcoma migratory ability through the MST1, MOB1 and YAP signaling cascades. Circular RNAs (circRNAs) serve as microRNAs (miRNAs) sponges to modulate expression of genes in various cancers. We found that the silencing of hsa_circ_0000004 and the upregulation of miR-1303 repressed APLN-induced cell migration and increases in PLOD2 expression. It appears that APLN promotes osteosarcoma migration by upregulating PLOD2 expression via the hippo signaling and by hsa_circ_0000004 binding with miR-1303. APLN shows potential as a therapeutic target in osteosarcoma metastasis. Osteosarcoma is a bone tumor primary malignancy. Lysyl hydroxylase 2 (LH2, encoded by the PLOD2 gene) is a major enzyme in modification of fibrotic collagen and enhancement of tumor cell metastasis. Apelin (APLN), an adipokine secreted by adipose tissue, is upregulated in different cancers and promotes angiogenesis, metastasis and cell proliferation, but its effects on osteosarcoma cell migration are uncertain. We therefore determined the function of APLN in the migration of human osteosarcoma cell lines 143B and MG63. Our finding showed that APLN expression levels in osteosarcoma tissue are higher than that in normal tissue. This study found that APLN induces osteosarcoma cell migration by promoting PLOD2 expression. Our investigations indicated that APLN enhances PLOD2 expression and the osteosarcoma migratory ability through the MST1, MOB1 and YAP signaling cascades. Circular RNAs (circRNAs) serve as microRNAs (miRNAs) sponges to modulate expression of genes in various cancers. We found that the silencing of hsa_circ_0000004 and the upregulation of miR-1303 repressed APLN-induced cell migration and increases in PLOD2 expression. It appears that APLN promotes osteosarcoma migration by upregulating PLOD2 expression via the hippo signaling and by hsa_circ_0000004 binding with miR-1303. APLN shows potential as a therapeutic target in osteosarcoma metastasis.
