Circular RNA circMRPS35 regulates progression and autophagy in osteosarcoma cells by recruiting KAT6B to govern FOXO3.

Osteosarcoma serves as frequently occurred bone malignancy that displays low survival rate and high incidence of metastasis. Circular RNAs (circRNAs) have been reported as the crucial molecules in osteosarcoma development. However, the effect of circRNA circMRPS35 on osteosarcoma remains unclear. Here, we aimed to explore the function of circMRPS35 in the regulation of autophagy and progression of osteosarcoma. The colony formation numbers and Edu-positive osteosarcoma cells were repressed by the overexpression of circMRPS35. Meanwhile, the overexpression of circMRPS35 increased the apoptosis rate of osteosarcoma cells. The expression levels of autophagy markers, including LC3 and Beclin1, were enhanced by the overexpression of circMRPS35 in osteosarcoma cells. Mechanically, the depletion of circMRPS35 reduced the enrichment of histone H3 lysine 23 acetylation (H3K23ac) on forkhead box O3 (FOXO3) promoter in osteosarcoma cells. The interaction of circMRPS35 and KAT6B was identified. The knockdown of KAT6B reduced the enrichment of H3K23ac on FOXO3 promoter in osteosarcoma cells. The depletion of circMRPS35 repressed the expression of FOXO3 in the MG63 and MNNG/HOS cells, whereas the overexpression of KAT6B reversed the effect. Significantly, KAT6B promotes apoptosis and autophagy of osteosarcoma cells. The overexpression of circMRPS35 induced the apoptosis and autophagy of osteosarcoma cells, in which the depletion of KAT6B or FOXO3 reversed the effect. The overexpression of circMRPS35 inhibited the tumor growth in vivo , whereas the depletion of KAT6B could reverse the effect in the mice. Therefore, we concluded that circRNA circMRPS35 repressed progression and induced autophagy of osteosarcoma cells.

Up-regulated lnc-SNHG1 contributes to osteosarcoma progression through sequestration of miR-577 and activation of WNT2B/Wnt/ß-catenin pathway.

Long noncoding RNA small nucleolar RNA host gene 1 (lnc-SNHG1) was reported to play an oncogenic role in the progression of cancers. However, the roles of SNHG1 and its molecular mechanism in osteosarcoma (OS) cells are largely unknown. In present study, we found that the expression of SNHG1 was up-regulated in OS tissues and cell lines. OS patients with the high SNHG1 expression were positively correlated with tumor size, TNM stage and lymph node metastasis. In addition, SNHG1 overexpression promoted cell proliferation, cell migration and EMT process in U2OS and MG63 cells and tumor growth in vivo. Furthermore, we also found that miR-577 could act as a ceRNAof SNHG1 in OS cells and the promotion of OS progression induced by lnc-SNHG1 overexpression required the inactivity of miR-577. Besides, we identified that WNT2B acted as a target of miR-577, and WNT2B played the oncogenic role in OS cells by activating Wnt/ß-catenin pathway. In short, our study suggested that lnc-SNHG1 could promote OS progression via miR-577 and WNT2B. The lnc-SNHG1/miR-577/WNT2B/Wnt/ß-catenin axis regulatory network might provide a potential new therapeutic strategy for OS treatment.

MicroRNA-208b inhibits human osteosarcoma progression by targeting ROR2.

MicroRNAs are widely involved in cancer progression by inhibiting the expression levels of oncogenes or tumor suppressor genes, and dysregulation of microRNAs may contribute to tumorigenesis. Here, we found that overexpressed miR-208b can reduce the proliferation of human osteosarcoma cell lines U-2OS and Saos-2 by arresting cell cycle progression. The in vivo xenograft tumors induced by Saos-2 cells overexpressing miR-208b had smaller size and grew more slowly than those induced by the control cells. The mobility of U-2OS or Saos-2 cells was also downregulated by miR-208b. MiR-208b targeted a site in the 3' untranslated region of receptor tyrosine kinase-like orphan receptor 2. Inhibition of receptor tyrosine kinase-like orphan receptor 2 suppresses osteosarcoma metastasis in vitro. Recovering the expression levels of receptor tyrosine kinase-like orphan receptor 2 in miR-208b-overexpressed U-2OS or Saos-2 cells attenuated the inhibitory effects of miR-208b. In addition, the expression levels of miR-208b are significantly reduced in human osteosarcoma tissue samples compared to normal tissue samples, and miR-208b levels correlated inversely with receptor tyrosine kinase-like orphan receptor 2 levels. On these bases, we identified that miR-208b targets receptor tyrosine kinase-like orphan receptor 2 gene by which miR-208b can regulate the development of osteosarcoma.