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Histone deacetylases (HDACs), initially described as histone modifiers, have more recently been verified to target various other proteins unrelated to the chromatin environment. On this basis, findings of the current study demonstrates that the pharmacological or genetic abrogation of HDAC6 in osteosarcoma cell lines down-regulates the expression of program death receptor ligand-1 (PD-L1), an important co-stimulatory molecule expressed in cancer cells, which activates the inhibitory regulatory pathway PD-1 in T cells. As shown by our results, the mechanism by which HDAC6 regulated PD-L1 expression was mediated by the transcription factor STAT3. In addition, we observed that selective HDAC6 inhibitors could inhibit tumor progression in vivo. Crucially, these results provide an essential pre-clinical rationale and justification for the necessity of further research on HDAC6 inhibitors as potential immuno-modulatory agents in osteosarcoma.

Dysregulation of miRNAs has been shown to contribute to multiple tumorigenic processes, as well as to correlate with tumour progression and prognosis. miR-199a has been shown to be dysregulated in multiple tumour types. However, the association between miR-199a and the chemoresistance features of osteosarcoma are not well understood, the target genes for miR-199a and the regulatory mechanisms are also unknown. In the present study, we demonstrated that miR-199a is expressed at low levels in osteosarcoma cells and patient samples. By the selection and establishment of cisplatin resistant osteosarcoma cell line, we observed a correlation between miR-199a and cisplatin resistance in osteosarcoma cells: resistant cells exhibit attenuated miR-199a expressions and exogenous overexpression of miR-199a sensitizes osteosarcoma cells to cisplatin. Moreover, we identified HIF-1α as a direct target for miR-199a. Intriguingly, cisplatin resistant osteosarcoma cells display significantly elevated HIF-1α expression under hypoxia. We report here overexpression of miR-199a resensitizes cisplatin resistant cells to cisplatin through inhibition of HIF-1α in vitro and in vivo. Finally, by analysing the clinical osteosarcoma patient samples, we demonstrate a reverse correlation between miR-199a and HIF-1α mRNAs. Our study will provide mechanisms for the miRNA-mediated anticancer therapy and miR-199a may be considered a promising therapeutic agent for osteosarcoma patients who fail to respond to conventional chemotherapy.

Background House dust mites are an important source of indoor allergens. More than 30 allergens of Dermatophagoides farinae ( D. farinae ) have been identified. Yet there may be many other allergens in mites remain to be characterized. Methods α-Tubulin (also named Der f 33) was cloned, expressed and purified. Reaction to specific-IgE, skin prick test and a mouse asthma model were employed to determine the allergenicity of Der f 33. Results The recombinant Der f 33 reacted to the serum of patients with mite allergy. The positive rate of skin prick test (SPT) was 23.5%. In an asthma mouse model, Der f 33 induced the airway allergy-like responses. Moreover, serum specific IgE and IgG1, interleukin-4 (IL-4) from bronchoalveolar lavage fluid (BALF) and spleen cell culture supernatant were markedly increased. In addition, Der f 33 upregulated the CD80 and TNF-α levels in dendritic cells (DCs). Conclusions Der f 33 is a novel allergen of D. farinae . It modulates the functions of DCs and induces airway allergy.