Conclusion
MIR31HG acts as an oncogene in OS for tumor progression via regulation of tumor suppressor miR-361 and its target genes.
Methods
OS tissues and adjacent non-tumor tissues (n=40) were collected to determine the expressions of MIR31HG by paired t-test. We here identified the miRNAs predicted to be bound to MIR31HG and investigated the impacts of MIR31HG on cell growth and metastasis of OS cells by CCK-8, flow cytometry, Transwell assay, Western blot, etc. in vitro and in vivo.
Purpose
Long noncoding RNA (LncRNA) containing microRNA host gene is an interesting type of LncRNA. MicroRNA-31 (miR-31)-host gene LncRNA (MIR31HG) have been recognized as an oncogene in many cancers, but not in osteosarcoma (OS). Interestingly, MIR31HG/miR-31 could not regulate each other's expression in certain cancer, suggesting that the role of MIR31HG in cancer is independent of miR-31. We here investigated the function and potential mechanism of MIR31HG in OS.
Results
MIR31HG was upregulated in OS tissues and OS cell lines. The patients with high expression of MIR31HG have high tumor stages and distant metastasis. Tumor suppressor miR-361, but not miR-31, was confirmed to be sponged directly by MIR31HG in OS cells and was down-regulated in OS cell lines. Knockdown of MIR31HG restored the expression of miR-361. Restoration of miR-361 level in Saos-2 and U2OS cells induced cell apoptosis and G1/S arrest, inhibited proliferation and migration, which was, however, abrogated by MIR31HG. Mechanistically, cell growth and metastasis-related target genes of MIR-361 including VEGF, FOXM1 and Twist were de-repressed in OS cells by MIR31HG overexpression, leading to upregulated BCL2, CCND1 and epithelial-mesenchymal transition (EMT) phenotype. Patients with high expression of MIR31HG also showed more VEGF, FOXM1 and Twist levels. Overexpression of MIR31HG in vivo also promoted tumor growth via inhibition of miR-361 signals and elevated the expression of VEGF, FOXM1 and Twist for tumor growth.