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bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis in vivo

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3950-3965页

作者： Linglong Deng Hannah Petrek Mei-Juan Tu Neelu Batra Ai-Xi Yu Ai-Ming Yu Department of Orthopaedic Trauma and Microsurgery Zhongnan Hospital of Wuhan UniversityWuhan 430072China Department of Biochemistry and Molecular Medicine UC Davis School of MedicineSacramentoCA 95817USA

With the understanding of microRNA(miRNA or miR) functions in tumor initiation,progression,and metastasis,efforts are underway to develop new miRNA-based *** recently,we demonstrated effectiveness of a novel humanized bioengineered miR-124-3 p prodrug in controlling spontaneous lung metastasis in mouse *** study was to investigate the molecular and cellular mechanisms by which miR-124-3 p controls tumor *** 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 *** them,plectin(PLEC) was verified as a new direct target for miR-124-3 p that links cytoskeleton components and *** 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 ***,miR-124-3 p sharply suppressed the formation of focal adhesion plaques,leading to reduced cell adhesion ***,efficacy and safety of biologic miR-124-3 p therapy was established in an aggressive experimental metastasis mouse model in *** 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.

关键词： RNA therapy MiR-124-3p Metastasis Proteomics Junctions Cell adhesion bioengineer Imaging

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Next generation of neurological therapeutics:Native and bioengineered extracellular vesicles derived from stem cells

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Asian Journal of Pharmaceutical Sciences 2022年第6期17卷 779-797页

作者： Shilin Jin Zhongyue Lv Lin Kang Jiayi Wang Chengcheng Tan Liming Shen Liang Wang Jing Liu Stem Cell Clinical Research Center National Joint Engineering LaboratoryThe First Affiliated Hospital of Dalian Medical UniversityDalian 116011China Liaoning Key Laboratory of Frontier Technology of Stem Cell and Precision Medicine Dalian Engineering Research Center for Genetic Variation Detection of Infectious Pathogenic MicroorganismsDalian Innovation Institute of Stem Cell and Precision MedicineDalian 116085China

Extracellular vesicles(EVs)-based cell-free therapy,particularly stem cell-derived extracellular vesicles(SC-EVs),offers new insights into treating a series of neurological disorders and becomes a promising candidate for alternative stem cell regenerative ***,SC-EVs are considered direct therapeutic agents by themselves and/or dynamic delivery systems as they have a similar regenerative capacity of stem cells to promote neurogenesis and can easily load many functional small molecules to recipient cells in the central nervous ***,as non-living entities,SC-EVs avoid the uncontrollability and manufacturability limitations of live stem cell products in vivo(e.g.,low survival rate,immune response,and tumorigenicity)and in vitro(e.g.,restricted sources,complex preparation processes,poor quality control,low storage,shipping instability,and ethical controversy)by strict quality control ***,SC-EVs can be engineered or designed to enhance further overall yield,increase bioactivity,improve targeting,and extend their ***,this review provides an overview on the biological properties of SC-EVs,and the current progress in the strategies of native or bioengineered SC-EVs for nerve injury repairing is *** we further summarize the challenges of recent research and perspectives for successful clinical application to advance SC-EVs from bench to bedside in neurological diseases.

关键词： Extracellular vesicles Stem cells Neurological disease Exosomes bioengineer

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