Objective: Many studies have shown that long non-coding RNAs (lncRNAs) are closely related to various cancers. This study aims to explore the roles of lncRNA HOXA11-AS in the development and progression of osteosarcoma (OS). Methods: The expression levels of HOXA11-AS and miR-125a-5p in tumor tissues and the adjacent tissues were detected by RT-PCR method. The proliferation, migration and invasion of MG-63 and KHOS cells were determined. Results: It was found that HOXA11-AS expression levels in OS tissues and OS cell lines were higher than those in OS adjacent tissues and normal human osteoblast cell lines. The higher expression level of HOXA11-AS was positively correlated with more severe clinical stage, distant metastasis and poor prognosis of OS. Inhibition of HOXA11-AS expression could reduce metastasis and invasion of OS cell lines. In addition, HOXA11-AS was found to be an endogenous inhibitor of miR-125a-5p, it down regulated the expression level of miR-125a-5p, and this process could promote the expression of Rab3D, the target gene of miR-125a-5p. Conclusion: Our study elucidated the role of a new HOXA11-AS/miR-125a-5p/Rab3D regulatory pathway in promoting OS metastasis.

Background/Aims: Osteosarcoma (OS) is commonly characterized by lower survival rates and high incidences of local recurrence due to its highly aggressive nature and metastatic tendencies. Studies have shown that histone deacetylase 4 (HDAC4) and proliferating cell nuclear antigen (PCNA) are highly expressed in cancers. Nevertheless, the roles of HDAC4 and PCNA in osteosarcoma (OS) remain unclear. This research aimed to study the expression of HDAC4 and PCNA and their relation to cell proliferation and invasion in human OS.Methods: The levels of HDAC4 and PCNA mRNA and protein were tested in human OS and osteochondroma (OC) tissues. The overexpression and knockdown of HDAC4 in OS cell lines were used to determine the effect of HDAC4 on the expression and degradation of PCNA. The effect of HDAC4 on cell proliferation, invasion and apoptosis was also detected. Additionally, we explored the interaction between HDAC4 and PCNA.Results: The results showed that both HDAC4 and PCNA were increased in human OS tissues. Overexpression of the HDAC4 protein increased the protein level of PCNA, had no effect on the PCNA mRNA level, and decreased the level of ubiquitinated PCNA. We found that overexpression of HDAC4 promoted cell proliferation and invasion and inhibited apoptosis. The opposite effects were observed when HDAC4 was knocked down. The results also showed that HDAC4 could bind to PCNA directly.Conclusions: Our findings suggest that HDAC4 could promote OS cell proliferation and invasion by regulating the expression of PCNA. Thus, our research indicates that HDAC4 may be a potential target for therapy in OS.

The authors have advised due to an error at the time of figure assembly, Figure 3B on page 4512 is incorrect. The correct Figure 3 is shown below.