Advanced

miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts

Pellegrino, Loredana; Stebbing, Justin; Braga, Vania M; Frampton, Adam E; Jacob, Jimmy; Buluwela, Lakjaya; Jiao, Long R; Periyasamy, Manikandan; Madsen, Chris D LU and Caley, Matthew P, et al. (2013) In Nucleic Acids Research 41(10). p.12-5400
Abstract

Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to... (More)

Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.

(Less)
Please use this url to cite or link to this publication:
@article{93b8c64c-1aa8-4991-a577-911dc00f2b1e,
  abstract     = {<p>Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.</p>},
  author       = {Pellegrino, Loredana and Stebbing, Justin and Braga, Vania M and Frampton, Adam E and Jacob, Jimmy and Buluwela, Lakjaya and Jiao, Long R and Periyasamy, Manikandan and Madsen, Chris D and Caley, Matthew P and Ottaviani, Silvia and Roca-Alonso, Laura and El-Bahrawy, Mona and Coombes, R Charles and Krell, Jonathan and Castellano, Leandro},
  issn         = {1362-4962},
  keyword      = {Animals,Breast Neoplasms,Cardiac Myosins,Cell Adhesion,Cell Line,Cell Line, Tumor,Cell Movement,Cytoskeletal Proteins,Cytoskeleton,Female,Focal Adhesions,Gene Expression Regulation, Neoplastic,Humans,Mice,Mice, Nude,MicroRNAs,Myosin Light Chains,Neoplasm Metastasis,Phosphorylation,Promoter Regions, Genetic,Pseudopodia,Transcription Factor AP-1,Transcription, Genetic,p21-Activated Kinases,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  number       = {10},
  pages        = {12--5400},
  publisher    = {Oxford University Press},
  series       = {Nucleic Acids Research},
  title        = {miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts},
  url          = {http://dx.doi.org/},
  volume       = {41},
  year         = {2013},
}