Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biologic...Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biological half-life,its contribution to pain response,and its inability to cross the blood-brain barrier.Considering that let-7(human miRNA)targets and regulates nerve growth factor,and that let-7 is a core regulator in peripheral nerve regeneration,we evaluated the possibilities of let-7 application in nerve repair.In this study,anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship,and functional screening.Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve,including Schwann cells,fibroblasts and macrophages.Use of hydrogel effectively achieved controlled,localized,and sustained delivery of let-7a antagomir.Finally,let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft,which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection.Our study provides an experimental basis for potential in vivo application of let-7a.展开更多
MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spin...MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spinal cord injury. This review summarizes the changes in expression levels of microRNAs after spinal cord injury. These aberrant changes suggest that microRNAs play an important role in inflammation, oxidative stress, apoptosis, glial scar formation and axonal regeneration. Given their small size and specificity of action, microRNAs could be potential therapeutics for treating spinal cord injury in the future. There are rapidly developing techniques for manipulating microRNA levels in animals; we review different chemical modification and delivery strategies. These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.展开更多
MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue specificity.miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression...MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue specificity.miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation, thus affecting various cellular processes.Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs.Recent evidence has shown that miRNA controls cell growth, apoptosis, and differentiation.Cancer is a complex genetic disease caused by abnormalities in gene structure and expression, moreover, miRNA expression correlates with cancers and could have a crucial function in tumor progression.Bioinformatic data indicate that each miRNA can control hundreds of target genes, but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to cancer process.展开更多
Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzin...Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC development.These findings provide a new perspective for the development of OSCC treatments.展开更多
Osteoclasts,which are derived from monocyte-macrophage precursors,are exclusive bone resorption cells.Limited evidence indicates that a class of small non-coding single-stranded RNAs known as“microRNAs”(miRNAs)is al...Osteoclasts,which are derived from monocyte-macrophage precursors,are exclusive bone resorption cells.Limited evidence indicates that a class of small non-coding single-stranded RNAs known as“microRNAs”(miRNAs)is also involved in bone resorption.Although various miRNAs regulate cell proliferation and differentiation,few miRNAs have been reported to play a key role in the regulation of osteoclast differentiation.In this short review,the biology and functional mechanisms of miRNAs in osteoclastogenesis are summarized.The profiling,function,and target prediction of miRNAs are discussed as well.展开更多
基金supported by the National Natural Science Foundation of China,No.31970968(to SYL)the Collegiate Natural Science Foundation of Jiangsu Province,No.16KJA310005(to SYL)+1 种基金Priority Academic Program Development of Jiangsu Higher Education Institutions[PAPD]the Natural Science Foundation of Jiangsu Province,No.BK20200976(to XHW).
文摘Neurotrophic factors,particularly nerve growth factor,enhance neuronal regeneration.However,the in vivo applications of nerve growth factor are largely limited by its intrinsic disadvantages,such as its short biological half-life,its contribution to pain response,and its inability to cross the blood-brain barrier.Considering that let-7(human miRNA)targets and regulates nerve growth factor,and that let-7 is a core regulator in peripheral nerve regeneration,we evaluated the possibilities of let-7 application in nerve repair.In this study,anti-let-7a was identified as the most suitable let-7 family molecule by analyses of endogenous expression and regulatory relationship,and functional screening.Let-7a antagomir demonstrated biosafety based on the results of in vivo safety assessments and it entered into the main cell types of the sciatic nerve,including Schwann cells,fibroblasts and macrophages.Use of hydrogel effectively achieved controlled,localized,and sustained delivery of let-7a antagomir.Finally,let-7a antagomir was integrated into chitosan conduit to construct a chitosan-hydrogel scaffold tissue-engineered nerve graft,which promoted nerve regeneration and functional recovery in a rat model of sciatic nerve transection.Our study provides an experimental basis for potential in vivo application of let-7a.
基金supported by grants from the National Natural Science Foundation of China,No. 30971633 and 31171045the Program for Changjiang Scholars and Innovative Research Team in University,No. IRT0935the New Jersey Commission on Spinal Cord Research
文摘MicroRNAs are a class of recently discovered, small non-coding RNAs that have been shown to play essential roles in a vast majority of biological processes. Very little is known about the role of microRNAs during spinal cord injury. This review summarizes the changes in expression levels of microRNAs after spinal cord injury. These aberrant changes suggest that microRNAs play an important role in inflammation, oxidative stress, apoptosis, glial scar formation and axonal regeneration. Given their small size and specificity of action, microRNAs could be potential therapeutics for treating spinal cord injury in the future. There are rapidly developing techniques for manipulating microRNA levels in animals; we review different chemical modification and delivery strategies. These may provide platforms for designing efficient microRNA delivery protocols for use in the clinic.
文摘MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that are involved in oncogenesis and show remarkable tissue specificity.miRNAs are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation, thus affecting various cellular processes.Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs.Recent evidence has shown that miRNA controls cell growth, apoptosis, and differentiation.Cancer is a complex genetic disease caused by abnormalities in gene structure and expression, moreover, miRNA expression correlates with cancers and could have a crucial function in tumor progression.Bioinformatic data indicate that each miRNA can control hundreds of target genes, but identification of the accurate miRNA targets will be crucial to exploit the emerging knowledge of miRNA contribution to cancer process.
基金supported by National Natural Science Foundation of China grants(Nos.82073000,51973136,81902779,and 82173326)Science Foundation of Sichuan Province(No.2022YFS0289,China)Interdisciplinary innovation project of West China College of Stomatology,Sichuan University(RD-03-202004,China).
文摘Circular RNAs(circRNAs)are ideal biomarkers of oral squamous cell carcinoma(OSCC)because of their highly stable closed-loop structure,and they can act as microRNA(miRNA)sponges to regulate OSCC progression.By analyzing clinical samples,we identified circCPNE1,a dysregulated circRNA in OSCC,and its expression level was negatively correlated with the clinical stage of OSCC patients.Gain-of-function assays revealed the tumor-suppressive effect of circCPNE1,which was then identified as a miR-330-3p sponge.MiR-330-3p was recognized as a tumor promoter in multiple studies,consistent with our finding that it could promote the proliferation,migration,and invasion of OSCC cells.These results indicated that selective inhibition of miR-330-3p could be an effective strategy to inhibit OSCC progression.Therefore,we designed cationic polylysine-cisplatin prodrugs to deliver antagomiR-330-3p(a miRNA inhibitory analog)via electrostatic interactions to form PP@miR nanoparticles(NPs).Paratumoral administration results revealed that PP@miR NPs effectively inhibited subcutaneous tumor progression and achieved partial tumor elimination(2/5),which confirmed the critical role of miR-330-3p in OSCC development.These findings provide a new perspective for the development of OSCC treatments.
文摘Osteoclasts,which are derived from monocyte-macrophage precursors,are exclusive bone resorption cells.Limited evidence indicates that a class of small non-coding single-stranded RNAs known as“microRNAs”(miRNAs)is also involved in bone resorption.Although various miRNAs regulate cell proliferation and differentiation,few miRNAs have been reported to play a key role in the regulation of osteoclast differentiation.In this short review,the biology and functional mechanisms of miRNAs in osteoclastogenesis are summarized.The profiling,function,and target prediction of miRNAs are discussed as well.
