miRs-134 and -370 function as tumor suppressors in colorectal cancer by independently suppressing EGFR and PI3K signalling

• Verfasst von: El-Daly, Sherien M. [VerfasserIn]
• Verfasst von: Abba, Mohammed L. [VerfasserIn]
• Verfasst von: Patil, Nitin [VerfasserIn]
• Verfasst von: Allgayer, Heike [VerfasserIn]
• Titel: miRs-134 and -370 function as tumor suppressors in colorectal cancer by independently suppressing EGFR and PI3K signalling
• Verf.angabe: Sherien M. El-Daly, Mohammed L. Abba, Nitin Patil and Heike Allgayer
• E-Jahr: 2016
• Jahr: 20 April 2016
• Umfang: 11 S.
• Fussnoten: Gesehen am 04.04.2019
• Titel Quelle: Enthalten in: Scientific reports
• Ort Quelle: [London] : Springer Nature, 2011
• Jahr Quelle: 2016
• Band/Heft Quelle: 6(2016) Artikel-Nummer 24720, 11 Seiten
• ISSN Quelle: 2045-2322
• DOI: doi:10.1038/srep24720
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1662805195

Abstract

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.