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Deng L, Petrek H, Tu MJ, et al. Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis . Acta Pharm Sin B. 2021;11(12):3950-3965doi: 10.1016/j.apsb.2021.07.027.
Deng, L., Petrek, H., Tu, M. J., Batra, N., Yu, A. X., & Yu, A. M. (2021). Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis . Acta pharmaceutica Sinica. B, 11(12), 3950-3965. https://doi.org/10.1016/j.apsb.2021.07.027
Deng, Linglong, et al. "Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis ." Acta pharmaceutica Sinica. B vol. 11,12 (2021): 3950-3965. doi: https://doi.org/10.1016/j.apsb.2021.07.027
Deng L, Petrek H, Tu MJ, Batra N, Yu AX, Yu AM. Bioengineered miR-124-3p prodrug selectively alters the proteome of human carcinoma cells to control multiple cellular components and lung metastasis . Acta Pharm Sin B. 2021 Dec;11(12):3950-3965. doi: 10.1016/j.apsb.2021.07.027. Epub 2021 Aug 17. PMID: 35024318; PMCID: PMC8727917.
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Acta Pharm Sin B. 2021 Dec;11(12):3950-3965. doi: 10.1016/j.apsb.2021.07.027. Epub 2021 Aug 17.

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

Acta pharmaceutica Sinica. B

Linglong Deng, Hannah Petrek, Mei-Juan Tu, Neelu Batra, Ai-Xi Yu, Ai-Ming Yu

Affiliations

  1. Department of Orthopaedic Trauma and Microsurgery, Zhongnan Hospital of Wuhan University, Wuhan 430072, China.
  2. Department of Biochemistry and Molecular Medicine, UC Davis School of Medicine, Sacramento, CA 95817, USA.

PMID: 35024318 PMCID: PMC8727917 DOI: 10.1016/j.apsb.2021.07.027

Abstract

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-124-3p prodrug in controlling spontaneous lung metastasis in mouse models. This study was to investigate the molecular and cellular mechanisms by which miR-124-3p controls tumor metastasis. Proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR-124-3p 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-124-3p that links cytoskeleton components and junctions. In miR-124-3p-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), cadherin 2 or N-cadherin (CDH2), and junctional adhesion molecule A (F11R or JAMA or JAM1) decreased, causing remodeling of cytoskeletons and disruption of cell-cell junctions. Furthermore, miR-124-3p sharply suppressed the formation of focal adhesion plaques, leading to reduced cell adhesion capacity. Additionally, efficacy and safety of biologic miR-124-3p therapy was established in an aggressive experimental metastasis mouse model

© 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

Keywords: Bioengineer; Cell adhesion; Imaging; Junctions; Metastasis; MiR-124-3p; Proteomics; RNA therapy

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