BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer...BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.展开更多
The differentiation shift from osteogenesis to adipogenesis of bone marrow mesenchymal stem cells(BMSCs)characterizes many pathological bone loss conditions.Stromal cell-derived factor-1(SDF1)is highly enriched in the...The differentiation shift from osteogenesis to adipogenesis of bone marrow mesenchymal stem cells(BMSCs)characterizes many pathological bone loss conditions.Stromal cell-derived factor-1(SDF1)is highly enriched in the bone marrow for C-X-C motif chemokine receptor 4(CXCR4)-positive hematopoietic stem cell(HSC)homing and tumor bone metastasis.In this study,we displayed CXCR4 on the surface of exosomes derived from genetically engineered NIH-3T3 cells.CXCR4+exosomes selectively accumulated in the bone marrow.Then,we fused CXCR4+exosomes with liposomes carrying antagomir-188 to produce hybrid nanoparticles(NPs).The hybrid NPs specifically gathered in the bone marrow and released antagomir-188,which promoted osteogenesis and inhibited adipogenesis of BMSCs and thereby reversed age-related trabecular bone loss and decreased cortical bone porosity in mice.Taken together,this study presents a novel way to obtain bone-targeted exosomes via surface display of CXCR4 and a promising anabolic therapeutic approach for age-related bone loss.展开更多
基金Supported by the National Natural Science Funds of China,No.81974448Guangdong Medical Research Foundation,No.B2019126Shenzhen Science and Technology Innovation Commission,No.JCYJ20210324135005013.
文摘BACKGROUND Altered miR-188-3p expression has been observed in various human cancers.AIM To investigate the miR-188-3p expression,its roles,and underlying molecular events in gastric cancer.METHODS Fifty gastric cancer and paired normal tissues were collected to analyze miR-188-3p and CBL expression.Normal and gastric cancer cells were used to manipulate miR-188-3p and CBL expression through different assays.The relationship between miR-188-3p and CBL was predicted bioinformatically and confirmed using a luciferase gene reporter assay.A Kaplan-Meier analysis was used to associate miR-188-3p or CBL expression with patient survival.A nude mouse tumor cell xenograft assay was used to confirm the in vitro data.RESULTS MiR-188-3p was found to be lower in the plasma of gastric cancer patients,tissues,and cell lines compared to their healthy counterparts.It was associated with overall survival of gastric cancer patients(P<0.001),tumor differentiation(P<0.001),lymph node metastasis(P=0.033),tumor node metastasis stage(I/II vs III/IV,P=0.024),and American Joint Committee on Cancer stage(I/II vs III/IV,P=0.03).Transfection with miR-188-3p mimics reduced tumor cell growth and invasion while inducing apoptosis and autophagy.CBL was identified as a direct target of miR-188-3p,with its expression antagonizing the effects of miR-188-3p on gastric cancer(GC)cell proliferation by inducing tumor cell apoptosis and autophagy through the inactivation of the Akt/mTOR signaling pathway.The in vivo data confirmed antitumor activity via CBL downregulation in gastric cancer.CONCLUSION The current data provides ex vivo,in vitro,and in vivo evidence that miR-188-3p acts as a tumor suppressor gene or possesses antitumor activity in GC.
基金This work was supported by grants from National Key R&D Program of China(No.2018YFC2001500)National Natural Science Foundation of China(No.91749204,81771491 to J.Su,and 81871099 to X.Chen).
文摘The differentiation shift from osteogenesis to adipogenesis of bone marrow mesenchymal stem cells(BMSCs)characterizes many pathological bone loss conditions.Stromal cell-derived factor-1(SDF1)is highly enriched in the bone marrow for C-X-C motif chemokine receptor 4(CXCR4)-positive hematopoietic stem cell(HSC)homing and tumor bone metastasis.In this study,we displayed CXCR4 on the surface of exosomes derived from genetically engineered NIH-3T3 cells.CXCR4+exosomes selectively accumulated in the bone marrow.Then,we fused CXCR4+exosomes with liposomes carrying antagomir-188 to produce hybrid nanoparticles(NPs).The hybrid NPs specifically gathered in the bone marrow and released antagomir-188,which promoted osteogenesis and inhibited adipogenesis of BMSCs and thereby reversed age-related trabecular bone loss and decreased cortical bone porosity in mice.Taken together,this study presents a novel way to obtain bone-targeted exosomes via surface display of CXCR4 and a promising anabolic therapeutic approach for age-related bone loss.
