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miRs-134 and -370 function as tumor suppressors in colorectal cancer by independently suppressing EGFR and PI3K signalling
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| Veröffentlicht in: | Scientific reports 6(2016) Artikel-Nummer 24720, 11 Seiten |
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| Personen und Körperschaften: | , , , |
| Titel: | miRs-134 and -370 function as tumor suppressors in colorectal cancer by independently suppressing EGFR and PI3K signalling/ Sherien M. El-Daly, Mohammed L. Abba, Nitin Patil and Heike Allgayer |
| Format: | E-Book-Kapitel |
| Sprache: | Englisch |
| veröffentlicht: |
20 April 2016
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| Gesamtaufnahme: |
: Scientific reports, 6(2016) Artikel-Nummer 24720, 11 Seiten
, volume:6 |
| Quelle: | Verbunddaten SWB Lizenzfreie Online-Ressourcen |
| Zusammenfassung: | 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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| Beschreibung: | Gesehen am 04.04.2019 |
| Umfang: | 11 |
| ISSN: |
2045-2322
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| DOI: | 10.1038/srep24720 |