Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/srep24720
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Funding
- Alfried Krupp von Bohlen und Halbach Foundation, Essen
- Dr Hella-Buehler-Foundation, Heidelberg
- Hector Foundation, Weinheim
- Dr Ingrid-zu-Solms Foundation, Frankfurt
- Walter Schulz Foundation, Munich
- Deutsche Krebshilfe Bonn [109558]
- DKFZ-MOST Cooperation, Heidelberg [CA149]
- HIPO/POP-Initiative for Personalized Oncology, Heidelberg [H032, H027]
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Growth factor receptor signalling plays a central and critical role in colorectal cancer. Most importantly, the EGFR signalling cascade involving PI3K/AKT/mTOR and Raf/MEK/ERK pathways are particularly relevant, since they are commonly activated in several cancer entities, including colorectal cancer. In this study, we show that miRs-134 and -370 are both capable of regulating these pathways by targeting EGFR and PIK3CA. In three different colorectal cancer cell lines (DLD1, HCT-116 and RKO), suppression of EGFR and PIK3CA through the enhanced expression of miR-134 or -370 led to a suppression of the key molecules of the PI3K/AKT/mTOR pathway. Furthermore, overexpression of miR-134 or -370 resulted in a significant reduction of cell proliferation, colony formation, migration, invasion and in-vivo tumor growth and metastasis. Concurrent experiments with small interfering RNAs targeting the prime targets show that our selected miRNAs exert a greater functional influence and affect more downstream molecules than is seen with silencing of the individual proteins. Taken together, these data indicate that miRs-134 and -370 are potential tumour suppressor miRNAs and could play a fundamental role in suppressing colorectal cancer tumorigenesis through their ability to co-ordinately regulate EGFR signalling cascade by independently targeting EGFR and PIK3CA.
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