Oncotarget

Research Papers:

MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells

Viviana Costa, Alessia Lo Dico, Aroldo Rizzo, Francesca Rajata, Marco Tripodi, Riccardo Alessandro and Alice Conigliaro _

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Oncotarget. 2017; 8:24292-24302. https://doi.org/10.18632/oncotarget.14464

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Abstract

Viviana Costa1,*, Alessia Lo Dico2,*, Aroldo Rizzo3, Francesca Rajata3, Marco Tripodi4,5, Riccardo Alessandro6,7,*, Alice Conigliaro4,*

1Innovative Technological Platforms for Tissue Engineering, Theranostic and Oncology, Rizzoli Orthopedic Institute, Palermo, Italy

2Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy

3Unità Operativa di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti “Villa Sofia-Cervello”, Palermo, Italy

4Dipartimento di Biotecnologie Cellulari ed Ematologia, Sapienza University of Rome, Rome, Italy

5National Institute for Infectious Diseases L. Spallanzani, IRCCS, Rome, Italy

6Dipartimento di Biopatologia e Biotecnologie Mediche, University of Palermo, Palermo, Italy

7Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council of Italy, Palermo, Italy

*These authors contributed equally to this work

Correspondence to:

Alice Conigliaro, email: [email protected]

Riccardo Alessandro, email: [email protected]

Keywords: miRNA675, CRC, EMT, metastasis, hypoxia

Received: November 16, 2016     Accepted: December 27, 2016     Published: January 03, 2017

ABSTRACT

The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1α, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1α; here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis.

Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1α induced EMT. MiR-675-5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1α and ii) and inhibiting Snail’s repressor DDB2 (Damage specific DNA Binding protein 2).

Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo, the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies.


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