MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to...MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.展开更多
Extracellular vesicles from skin-derived precursor Schwann cells(SKP-SC-EVs)promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats.This study aimed at expanding the application of SKPSC...Extracellular vesicles from skin-derived precursor Schwann cells(SKP-SC-EVs)promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats.This study aimed at expanding the application of SKPSC-EVs in nerve grafting by creating a chitosan/PLGA-based,SKP-SC-EVs-containing tissue engineered nerve graft(TENG)to bridge a 40-mm long sciatic nerve defect in dogs.SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions,supported the outgrowth and myelination of regenerated axons,and alleviated the denervation-induced atrophy of target muscles in dogs.To clarify the underlying molecular mechanism,we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons,and miR-30b-5p was the most important among others.We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK,STAT3 or CREB.Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.展开更多
基金supported by Correlation between RECK and GH-type pituitary adenomas(No.21JR11RE027).
文摘MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.
基金supported by the Major Research Plan of the National Natural Science Foundation of China(92068112)the National Key Research and Development Program of China(2017YFA0104700)+1 种基金the National Natural Science Foundation of China(82201509)the National Major Project of Research and Development(2022YFA1105500).
文摘Extracellular vesicles from skin-derived precursor Schwann cells(SKP-SC-EVs)promote neurite outgrowth in culture and enhance peripheral nerve regeneration in rats.This study aimed at expanding the application of SKPSC-EVs in nerve grafting by creating a chitosan/PLGA-based,SKP-SC-EVs-containing tissue engineered nerve graft(TENG)to bridge a 40-mm long sciatic nerve defect in dogs.SKP-SC-EVs contained in TENGs significantly accelerated the recovery of hind limb motor and electrophysiological functions,supported the outgrowth and myelination of regenerated axons,and alleviated the denervation-induced atrophy of target muscles in dogs.To clarify the underlying molecular mechanism,we observed that SKP-SC-EVs were rich in a variety of miRNAs linked to the axon growth of neurons,and miR-30b-5p was the most important among others.We further noted that miR-30b-5p contained within SKP-SC-EVs exerted nerve regeneration-promoting effects by targeting the Sin3a/HDAC complex and activating the phosphorylation of ERK,STAT3 or CREB.Our findings suggested that SKP-SC-EVs-incorporating TENGs represent a novel type of bioactive material with potential application for peripheral nerve repair in the clinic.