The present study aims to discuss the effects of miR-27a and its target gene secreted frizzled related protein 1 (<i>SFRP1</i>) on proliferation and invasion of human osteosarcoma cells via Wnt/β-catenin signaling pathway.
As a result, the miRNA-TF-mRNA regulatory network, including 1049 nodes (516 miRNA, 25 TFs, and 508 DEGs) and 15942 edges (interaction relationships, such as Pparg-Abca1 and miR-590-3p-AXIN2), was constructed, from which three significant modules were extracted and modules 2 and 3 contained interactions between miRNAs/TFs and DEGs such as miR-103-3p-<i>AXIN2</i>, miR-124-3p-<i>AR</i>-<i>Tgfb1i1</i>, and miR-27a-3p-<i>PPARG</i>-<i>Abca1</i>. miR-27a-3p was a known miRNA associated with OS.
In order to explore the role of miR‑27a‑3p in the development and progression of osteosarcoma, the expression of miR‑27a‑3p was inhibited by transfection of the MG-63 cells with miR‑27a‑3p inhibitor.
In total, 761 overlapping genes in 987 CNV regions and in the genes in 7,313 miRNA-gene pairs were obtained. miRNAs (hsa-miR-27a-3p, hsa-miR-124-3p, hsa-miR-9-5p, hsa-miR-182-5p, hsa-miR-26a-5p) and the genes [Fibroblast growth factor receptor substrate 2 (<i>FRS2</i>), coronin 1C (<i>CORO1C</i>), forkhead box P1 (<i>FOXP1</i>), cytoplasmic polyadenylation element binding protein 4 (<i>CPEB4</i>) and glucocorticoid induced 1 (<i>GLCCI1</i>)] with the highest degrees of association with osteosarcoma development were identified.
These findings establish that miR-27a/miR-27a* pair plays a significant role in OS metastasis and proposes it as a potential diagnostic and therapeutic target in managing OS metastases.
Then, high miR-27a expression was more frequently occurred in osteosarcoma patients with advanced clinical stage (P=0.001), positive distant metastasis (P=0.01) and poor response to chemotherapy (P=0.008).
In vitro and in vivo functional validation in osteosarcoma cell lines confirmed the tumor suppressive role of miR-16 and the pro-metastatic role of miR-27a.