MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer

Nicola Valeri, Chiara Braconi, Pierluigi Gasparini, Claudio Murgia, Andrea Lampis, Viola Paulus-Hock, Jonathan R. Hart, Lynn Ueno, Sergei I. Grivennikov, Francesca Lovat, Alessio Paone, Luciano Cascione, Khlea M. Sumani, Angelo Veronese, Muller Fabbri, Stefania Carasi, Hansjuerg Alder, Giovanni Lanza, Roberta Gafa', Mary P. MoyerRachel A. Ridgway, Julia Cordero, Gerard J. Nuovo, Wendy L. Frankel, Massimo Rugge, Matteo Fassan, Joanna Groden, Peter K. Vogt, Michael Karin, Owen J. Sansom, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

256 Scopus citations

Abstract

MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether itrepresents a bystander event or actually drives tumor progression invivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment.

Original languageEnglish (US)
Pages (from-to)469-483
Number of pages15
JournalCancer Cell
Volume25
Issue number4
DOIs
StatePublished - Apr 14 2014
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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