Junctional adhesion molecule-A(JAM-A),also known as the F11 receptor(F11R),is one of the tight junction components.JAM-A is a transmembrane glycoprotein that regulates many cellular processes,i.e.,angiogenesis,leukocy...Junctional adhesion molecule-A(JAM-A),also known as the F11 receptor(F11R),is one of the tight junction components.JAM-A is a transmembrane glycoprotein that regulates many cellular processes,i.e.,angiogenesis,leukocyte transendothelial migration,intercellular permeability,epithelial-to-mesenchymal transition,and platelet activation.Of note,it is involved in the pathogenesis of various cancer types,including gynecological cancers.Only a few studies are available about this cancer type.Observed aberrant JAM-A expression in gynecological cancers correlates with poor patient prognosis.To the best of our knowledge,conflicting JAM-A roles in various cancer types suggest that its involvement is complex and tumor-type specific.The underlying molecular mechanisms and pathways responsible for JAM-A functions were not fully elucidated and need to be identified.Finding appropriate novel molecular cancer biomarkers may reduce observed very high mortality rates and could contribute to personalized treatment development.The main aim of the present viewpoint article is to report the current knowledge about JAM-A participation in gynecological malignancies.展开更多
MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast canc...MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR （qRT-PCR）. Junctional adhesion molecule A （JAM-A） was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-offunction assays, and the inhibition of JAM-A by miR- 495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-4g5 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.展开更多
The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identif...The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.展开更多
Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yi...Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.展开更多
文摘Junctional adhesion molecule-A(JAM-A),also known as the F11 receptor(F11R),is one of the tight junction components.JAM-A is a transmembrane glycoprotein that regulates many cellular processes,i.e.,angiogenesis,leukocyte transendothelial migration,intercellular permeability,epithelial-to-mesenchymal transition,and platelet activation.Of note,it is involved in the pathogenesis of various cancer types,including gynecological cancers.Only a few studies are available about this cancer type.Observed aberrant JAM-A expression in gynecological cancers correlates with poor patient prognosis.To the best of our knowledge,conflicting JAM-A roles in various cancer types suggest that its involvement is complex and tumor-type specific.The underlying molecular mechanisms and pathways responsible for JAM-A functions were not fully elucidated and need to be identified.Finding appropriate novel molecular cancer biomarkers may reduce observed very high mortality rates and could contribute to personalized treatment development.The main aim of the present viewpoint article is to report the current knowledge about JAM-A participation in gynecological malignancies.
文摘MicroRNAs （miRNAs） are small, non-coding RNAs that function as post-transcriptional regulators of gene expression. The deregulated expression of miRNAs is associated with a variety of diseases, including breast cancer. In the present study, we found that miR-495 was markedly up-regulated in clinical breast cancer samples by quantitative real time-PCR （qRT-PCR）. Junctional adhesion molecule A （JAM-A） was predicted to be a potential target of miR-495 by bioinformatics analysis and was subsequently verified by luciferase assay and Western blotting. JAM-A was found to be negatively correlated with the migration of breast cancer cells through loss-of-function and gain-offunction assays, and the inhibition of JAM-A by miR- 495 promoted the migration of MCF-7 and MDA-MB-231 cells. Furthermore, overexpression of JAM-A could restore miR-495-induced breast cancer cell migration. Taken together, our findings suggest that miR-4g5 could facilitate breast cancer progression through the repression of JAM-A, making this miRNA a potential therapeutic target.
基金supported by the National Natural Science Foundation of China(Grants No.81772075,81772076,and 32071186).
文摘The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.
基金supported by the Featured Clinical Discipline Project of Shanghai Pudong Fund(Grant No.PWYts2021-07)the East Hospital Affiliated to Tongji University Introduced Talent Research Startup Fund(Grant No.DFRC2019008)the National Natural Science Foundation of China(Grant No.32071186).
文摘Androgenic alopecia(AGA)is a highly prevalent form of non-scarring alopecia but lacks effective treatments.Stem cell exosomes have similar repair effects to stem cells,suffer from the drawbacks of high cost and low yield yet.Cell-derived nanovesicles acquired through mechanical extrusion exhibit favorable biomimetic properties similar to exosomes,enabling them to efficiently encapsulate substantial quantities of therapeutic proteins.In this study,we observed that JAM-A,an adhesion protein,resulted in a significantly increased the adhesion and resilience of dermal papilla cells to form snap structures against damage caused by dihydrotestosterone and macrophages,thereby facilitating the process of hair regrowth in cases of AGA.Consequently,adipose-derived stem cells were modified to overexpress JAM-A to produce engineered JAM-A overexpressing nanovesicles(JAM-A^(OE)@NV).The incorporation of JAM-A^(OE)@NV into a thermosensitive hydrogel matrix(JAM-A^(OE)@NV Gel)to effectively addresses the limitations associated with the short half-life of JAM-A^(OE)@NV,and resulted in the achievement of a sustained-release profile for JAM-A^(OE)@NV.The physicochemical characteristics of the JAM-A^(OE)@NV Gel were analyzed and assessed for its efficacy in promoting hair regrowth in vivo and vitro.The JAM-A^(OE)@NV Gel,thus,presents a novel therapeutic approach and theoretical framework for promoting the treatment of low cell adhesion diseases similar to AGA.
