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 c...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.展开更多
Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impede...Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.展开更多
Although cartilage tissue engineering has been developed for decades, it is still unclear whether angio- genesis was the accompaniment of chondrogenesis in cartilage regeneration. This study aimed to explore the proce...Although cartilage tissue engineering has been developed for decades, it is still unclear whether angio- genesis was the accompaniment of chondrogenesis in cartilage regeneration. This study aimed to explore the process of anti-angiogenesis during cartilage regenerative progress in cartilage repair extracellular matrix (ECM) materials under Hypoxia. C3H10T1/2 cell line, seeded as pellet or in ECM materials, was added with chondrogenic medium or DMEM medium for 21 days under hypoxia or normoxia environment. Genes and miRNAs related with chondrogenesis and angiogenesis were detected by RT-qPCR technique on Days 7, 14, and 21. Dual-luciferase report system was used to explore the regulating roles of miRNAs on angiogenesis. Results showed that the chondrogenic medium promotes chondrogenesis both in pellet and ECM materials culture. HIF1α was up-regulated under hypoxia compared with normoxia (P 〈 0.05). Meanwhile, hypoxia enhanced chondrogenesis, miR-140-Sp exhibited higher expression while miR-146b exhibited lower expression. The chondrogenic phenotype was more stabilized in the ECM materials in chondrogenic medium than DMEM medium, with lower VEGFα expression even under hypoxia. Dual-luciferase report assays demonstrated that miR-140-5p directly targets VEGFct by binding its 3'- UTR. Taken together, chondrogenic cytokines, ECM materials and hypoxia synergistically promoted chondrogenesis and inhibited angiogenesis, miR-140-5p olaved an imnortant role in this process.展开更多
基金supported by grants from the National Natural Science Foundation of China(81802184)the Natural Science Foundation of Guangdong Province(2017A030310226)the Fundamental Research Funds for the Central Universities(19ykpy22).
文摘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.
基金This work was supported by the Natural Science Foundation of Guangdong Province,China(No.2017A030313889)This work was partly supported by National Natural Science Foundation of China(No.81772368)the Science and Technology Planning Project of Guangdong Province(No.2017B090912007).
文摘Severe burns are challenging to heal and result in significant death throughout the world.Adiposederived mesenchymal stem cells(ADSCs)have emerged as a promising treatment for fullthickness burn healing but are impeded by their low viability and efficiency after grafting in vivo.Nitric oxide(NO)is beneficial in promoting stem cell bioactivity,but whether it can function effectively in vivo is still largely unknown.In this study,we bioprinted an efficient biological scaffold loaded with ADSCs and NO(3D-ADSCs/NO)to evaluate its biological efficacy in promoting severe burn wound healing.The integral 3D-ADSCs/NO hydrogel scaffolds were constructed via 3D bioprinting.Our results shown that 3D-ADSCs/NO can enhance the migration and angiogenesis of Human Umbilical Vein Endothelial Cells(HUVECs).Burn wound healing experiments in mice revealed that 3D-ADSCs/NO accelerated the wound healing by promoting faster epithelialization and collagen deposition.Notably,immunohistochemistry of CD31 suggested an increase in neovascularization,supported by the upregulation of vascular endothelial growth factor(VEGF)mRNA in ADSCs in the 3D biosystem.These findings indicated that 3D-ADSC/NO hydrogel scaffold can promote severe burn wound healing through increased neovascularization via the VEGF signalling pathway.This scaffold may be considered a promising strategy for healing severe burns.
基金supported by the National Basic Research Program of China(973 Program,No.2012CB619100)the National Natural Science Foundation of China(Nos.31430030,0731001,and 81071512)+1 种基金the Natural Science Foundation of Guangdong Province(No.2014A030310466)the China Scholarship Council
文摘Although cartilage tissue engineering has been developed for decades, it is still unclear whether angio- genesis was the accompaniment of chondrogenesis in cartilage regeneration. This study aimed to explore the process of anti-angiogenesis during cartilage regenerative progress in cartilage repair extracellular matrix (ECM) materials under Hypoxia. C3H10T1/2 cell line, seeded as pellet or in ECM materials, was added with chondrogenic medium or DMEM medium for 21 days under hypoxia or normoxia environment. Genes and miRNAs related with chondrogenesis and angiogenesis were detected by RT-qPCR technique on Days 7, 14, and 21. Dual-luciferase report system was used to explore the regulating roles of miRNAs on angiogenesis. Results showed that the chondrogenic medium promotes chondrogenesis both in pellet and ECM materials culture. HIF1α was up-regulated under hypoxia compared with normoxia (P 〈 0.05). Meanwhile, hypoxia enhanced chondrogenesis, miR-140-Sp exhibited higher expression while miR-146b exhibited lower expression. The chondrogenic phenotype was more stabilized in the ECM materials in chondrogenic medium than DMEM medium, with lower VEGFα expression even under hypoxia. Dual-luciferase report assays demonstrated that miR-140-5p directly targets VEGFct by binding its 3'- UTR. Taken together, chondrogenic cytokines, ECM materials and hypoxia synergistically promoted chondrogenesis and inhibited angiogenesis, miR-140-5p olaved an imnortant role in this process.