miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β. Academic Article uri icon

Overview

MeSH

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Female
  • Fluorescent Antibody Technique
  • HCT116 Cells
  • HT29 Cells
  • Homeodomain Proteins
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • SOXC Transcription Factors
  • Smad7 Protein
  • Transcription Factors
  • Young Adult

MeSH Major

  • Colorectal Neoplasms
  • Feedback, Physiological
  • MicroRNAs
  • Neoplasm Recurrence, Local
  • Transforming Growth Factor beta

abstract

  • As patient survival drops precipitously from early-stage cancers to late-stage and metastatic cancers, microRNAs that promote relapse and metastasis can serve as prognostic and predictive markers as well as therapeutic targets for chemoprevention. Here we show that miR-1269a promotes colorectal cancer (CRC) metastasis and forms a positive feedback loop with TGF-β signalling. miR-1269a is upregulated in late-stage CRCs, and long-term monitoring of 100 stage II CRC patients revealed that miR-1269a expression in their surgically removed primary tumours is strongly associated with risk of CRC relapse and metastasis. Consistent with clinical observations, miR-1269a significantly increases the ability of CRC cells to invade and metastasize in vivo. TGF-β activates miR-1269 via Sox4, while miR-1269a enhances TGF-β signalling by targeting Smad7 and HOXD10, hence forming a positive feedback loop. Our findings suggest that miR-1269a is a potential marker to inform adjuvant chemotherapy decisions for CRC patients and a potential therapeutic target to deter metastasis.

publication date

  • April 15, 2015

has subject area

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Chromatin Immunoprecipitation
  • Colorectal Neoplasms
  • Feedback, Physiological
  • Female
  • Fluorescent Antibody Technique
  • HCT116 Cells
  • HT29 Cells
  • Homeodomain Proteins
  • Humans
  • Male
  • Mice
  • MicroRNAs
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • SOXC Transcription Factors
  • Smad7 Protein
  • Transcription Factors
  • Transforming Growth Factor beta
  • Young Adult

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4399006

Digital Object Identifier (DOI)

  • 10.1038/ncomms7879

PubMed ID

  • 25872451

Additional Document Info

start page

  • 6879

volume

  • 6