Hsa_circ_0002137 stabled by LIN28B promotes osteosarcoma cell growth through the hsa-miR-1246/BCL2 axis

Circular RNAs(circRNAs)are a novel class of non-coding RNA that have recently shown to have huge capabilities in the regulation of gene expression at the posttranscriptional level.Growing evidence has indicated that circRNAs could serve as competing endogenous RNAs(ceRNAs)to sponge microRNAs(miRNAs)and suppress functions of targeted miRNAs.Osteosarcoma(OS)is the most common malignant primary bone cancer.Hsa_circ_0002137 is upregulated in OS.However,the role of hsa_circ_0002137 in OS remains unclear.Using miRNA pull-down assay,we showed that cir_0002137 sponged hsa-miR-1246,and BCL2 apoptosis regulator(BCL2)mRNA was a potential target of hsa-miR-1246 in human osteosarcoma(HOS)cells.Further,we found that hsa_cir_0002137 could enhance the expression of BCL2 hsa-miR-1246 and promote HOS cell growth through sponging hsa-miR-1246.Moreover,RNA binding protein immunoprecip itation(RIP)assay revealed that lin-28 homolog B(LIN28B)protein associated with hsa_circ_0002137,and LIN28B could increase hsa_circ_0002137 stability and thus accelerate OS cell growth.Our work was the first to study the functions of hsa_circ_0002137,has-miR-1246 and LIN28B in OS,and these results may provide novel therapeutic targets for OS treatment.

Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation

Joint contracture is a fibrotic complication induced by joint immobilization and trauma,which is characterized as excessive myofibroblast proliferation in joint capsule.The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction.Our previous study has shown that curcumin can inhibit myofibroblast proliferation in vitro,but the major challenge is the low aqueous solubility and biological activity of curcumin.In this study,hyaluronic acid-curcumin(HA-Cur)conjugate was synthesized to suppress myofibroblasts in joint contracture.Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-b(TGF-b).The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry,reverse transcription-quantitative polymerase chain reaction(PCR),methylation-specific PCR,western blot,transwell migration assay and proliferation assay.Results showed that 30 lM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracture in vitro by regulating the methylation of prostaglandin E receptor 2(PTGER2)and inhibiting TGF-b signaling.This may provide a mechanism for the treatment of joint contracture,and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.