title: miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β.
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.
authors: 1] School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA [2] Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Pengcheng
authors: P
authors: Bu
authors: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Lihua
authors: L
authors: Wang
authors: School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Kai-Yuan
authors: KY
authors: Chen
authors: School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Nikolai
authors: N
authors: Rakhilin
authors: 1] Departments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, New York 10021, USA [2] Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10021, USA.
authors: Jian
authors: J
authors: Sun
authors: 1] Department of Clinical Sciences, University of Barcelona, Barcelona 08193, Spain [2] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP, Barcelona E08907, Spain.
authors: Adria
authors: A
authors: Closa
authors: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Kuei-Ling
authors: KL
authors: Tung
authors: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Sarah
authors: S
authors: King
authors: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Anastasia
authors: A
authors: Kristine Varanko
authors: Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Yitian
authors: Y
authors: Xu
authors: Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Joyce
authors: J
authors: Huan Chen
authors: Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina 27710, USA.
authors: Amelia S
authors: AS
authors: Zessin
authors: School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: James
authors: J
authors: Shealy
authors: Department of Biomedical Sciences, Cornell University, Ithaca, New York 14853, USA.
authors: Bethany
authors: B
authors: Cummings
authors: Division of Medical Oncology, Duke Cancer Institute, Duke University, Durham, North Carolina 27710, USA.
authors: David
authors: D
authors: Hsu
authors: Departments of Medicine, Genetic Medicine and Surgery, Weill Cornell Medical College, New York, New York 10021, USA.
authors: Steven M
authors: SM
authors: Lipkin
authors: 1] Department of Clinical Sciences, University of Barcelona, Barcelona 08193, Spain [2] Cancer Prevention and Control Program, Catalan Institute of Oncology-IDIBELL, CIBERESP, Barcelona E08907, Spain.
authors: Victor
authors: V
authors: Moreno
authors: 1] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10065, USA [2] Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, New York 10065, USA.
authors: Zeynep H
authors: ZH
authors: Gümüş
authors: 1] School of Electrical and Computer Engineering, Cornell University, Ithaca, New York 14853, USA [2] Department of Biomedical Engineering, Cornell University, Ithaca, New York 14853, USA [3] Department of Biological and Environmental Engineering, Cornell University, Ithaca, New York 14853, USA.
authors: Xiling
authors: X
authors: Shen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D025461:Feedback, Physiological; D005260:Female; D005455:Fluorescent Antibody Technique; D045325:HCT116 Cells; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009368:Neoplasm Transplantation; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D055751:SOXC Transcription Factors / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; C000600169:MIRN1269 microRNA, human; D035683:MicroRNAs; C497806:SMAD7 protein, human; C083431:SOX4 protein, human; D055751:SOXC Transcription Factors; D051906:Smad7 Protein; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C072064:HOXD10 protein, human