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MiR‐124‐3p signaling in the control of metastasis‐related cytoskeleton organization, cell junctions and adhesion
Author(s) -
Deng Linglong,
Petrek Hannah,
Tu MeiJuan,
Yu AiMing
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02586
Subject(s) - microbiology and biotechnology , cell adhesion , cytoskeleton , focal adhesion , cadherin , metastasis , cell adhesion molecule , actin cytoskeleton , cell , chemistry , biology , signal transduction , cancer , biochemistry , genetics
Our recent studies using novel bioengineered miR‐124‐3p molecules have demonstrated the functions of miR‐124‐3p in the inhibition of human osteosarcoma cell invasiveness in vitro and lung metastasis in vivo . This study is to investigate the molecular and cellular mechanisms by which miR‐124‐3p controls tumor metastasis. LC‐MS‐based proteomics study identified a set of proteins selectively and significantly downregulated by bioengineered miR‐124‐3p, which were assembled into multiple biological pathways critical for cancer, such as cell junctions and focal adhesion. Among these proteins, we identified and verified plectin (PLEC) as a new direct target for miR‐124‐3p that links cytoskeleton to intercellular junctions. Associated with significantly lower levels of PLEC, ITGB1, IQGAP1 and CDH2 proteins in miR‐124‐3p‐treated human osteosarcoma 143B and MG63 cells as well as NSCLC A549 cells, cytoskeleton was remodeled and cell‐cell junctions were sharply inhibited. Furthermore, miR‐124‐3p decreased the ability of cells to form focal adhesion complexes and plaques, leading to much lower levels of cell adhesion capacity. Together, our results connect miR‐124‐3p‐PLEC to other known elements in the control of cytoskeleton, cell adhesion and junctions essential for cancer cell invasion and extravasation towards metastasis.