With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a nove...With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a novel humanized bioengineered miR-124-3 p prodrug in controlling spontaneous lung metastasis in mouse models.This study was to investigate the molecular and cellular mechanisms by which miR-124-3 p controls tumor metastasis.Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3 p in A549 cells,which were assembled into multiple cellular components critical for metastatic potential.Among them,plectin(PLEC) was verified as a new direct target for miR-124-3 p that links cytoskeleton components and junctions.In miR-124-3 p-treated lung cancer and osteosarcoma cells,protein levels of vimentin,talin 1(TLN1),integrin beta-1(ITGB1),IQ motif containing GTPase activating protein 1(IQGAP1),cadherin2 or N-cadherin(CDH2),and junctional adhesion molecule A(F11 R or JAMA or JAM1) decreased,causing remodeling of cytoskeletons and disruption of cell-cell junctions.Furthermore,miR-124-3 p sharply suppressed the formation of focal adhesion plaques,leading to reduced cell adhesion capacity.Additionally,efficacy and safety of biologic miR-124-3 p therapy was established in an aggressive experimental metastasis mouse model in vivo.These results connect miR-124-3 p-PLEC signaling to other elements in the control of cytoskeleton,cell junctions,and adhesion essential for cancer cell invasion and extravasation towards metastasis,and support the promise of miR-124 therapy.展开更多
The authors regret that there was one incorrect image used within Fig.4A,143B cells treated with LSA at 24 h time point,which was obtained from vehicle group but mislabelled as LSA in the publication.In our studies,th...The authors regret that there was one incorrect image used within Fig.4A,143B cells treated with LSA at 24 h time point,which was obtained from vehicle group but mislabelled as LSA in the publication.In our studies,three biological replicates were included in each treatment group and at least three images were taken for different fields of each sample.We thus selected a correct representative image from the LSA treated 143B cells at 24 h time point to replace that mislabelled image,and the updated Fig.4 is provided below.The authors apologize for any inconvenience caused to the journal and readers,while this correction does not affect any results and conclusions.The authors have provided the original data of this figure to Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.展开更多
基金supported by the National Cancer Institute (No. R01CA225958 to Ai-Ming Yu, USA)National Institutes of Health+3 种基金supported by Hubei Province Scientific and Technological Innovation Key Project (No. 2019ACA136, China)Hubei Province Medical Leader Talent Project (No. LJ20200405, China)supported by a fellowship from the Chinese Scholarship Council (No. 201906270202, China)the Mouse Biology and Molecular Pharmacology Shared Resources funded by the UC Davis Comprehensive Cancer Center Support Grant awarded by the National Cancer Institute (No. P30CA093373, USA), National Institutes of Health。
文摘With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based therapies.Very recently,we demonstrated effectiveness of a novel humanized bioengineered miR-124-3 p prodrug in controlling spontaneous lung metastasis in mouse models.This study was to investigate the molecular and cellular mechanisms by which miR-124-3 p controls tumor metastasis.Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3 p in A549 cells,which were assembled into multiple cellular components critical for metastatic potential.Among them,plectin(PLEC) was verified as a new direct target for miR-124-3 p that links cytoskeleton components and junctions.In miR-124-3 p-treated lung cancer and osteosarcoma cells,protein levels of vimentin,talin 1(TLN1),integrin beta-1(ITGB1),IQ motif containing GTPase activating protein 1(IQGAP1),cadherin2 or N-cadherin(CDH2),and junctional adhesion molecule A(F11 R or JAMA or JAM1) decreased,causing remodeling of cytoskeletons and disruption of cell-cell junctions.Furthermore,miR-124-3 p sharply suppressed the formation of focal adhesion plaques,leading to reduced cell adhesion capacity.Additionally,efficacy and safety of biologic miR-124-3 p therapy was established in an aggressive experimental metastasis mouse model in vivo.These results connect miR-124-3 p-PLEC signaling to other elements in the control of cytoskeleton,cell junctions,and adhesion essential for cancer cell invasion and extravasation towards metastasis,and support the promise of miR-124 therapy.
文摘The authors regret that there was one incorrect image used within Fig.4A,143B cells treated with LSA at 24 h time point,which was obtained from vehicle group but mislabelled as LSA in the publication.In our studies,three biological replicates were included in each treatment group and at least three images were taken for different fields of each sample.We thus selected a correct representative image from the LSA treated 143B cells at 24 h time point to replace that mislabelled image,and the updated Fig.4 is provided below.The authors apologize for any inconvenience caused to the journal and readers,while this correction does not affect any results and conclusions.The authors have provided the original data of this figure to Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.
