c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2.

Titlec-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2.
Publication TypeJournal Article
Year of Publication2013
AuthorsLi X, Liu X, Xu W, Zhou P, Gao P, Jiang S, Lobie PE, Zhu T
JournalThe Journal of biological chemistry
Volume288
Issue25
Pagination18121-33
Date Published2013 Jun 21
Abstract

Emerging evidence indicates that the miR-23a/24-2/27a cluster may possess a causal role in mammary tumorigenesis and function as a novel class of oncogenes. However, the regulatory mechanism of the miR-23a/24-2/27a cluster in mammary carcinoma cell invasion and migration is still largely unknown. We observed that the expression levels of miR-23a, miR-24-2 and miR-27a were significantly higher in breast cancer with lymph node metastasis, compared with that from patients without lymph node metastasis or normal tissue. Forced expression of the miR-23a/24-2/27a cluster promoted mammary carcinoma cell migration, invasion, and hepatic metastasis, through targeting Sprouty2 (SPRY2) and consequent activation of p44/42 MAPK. Epidermal growth factor induced the expression of the transcription factor c-MYC, which promoted the expression of mature miR-23a, miR-24-2, and miR-27a and subsequently decreased expression of SPRY2 and activated p44/42 MAPK to promote mammary carcinoma cell migration and invasion. We therefore suggest a novel link between epidermal growth factor and the miR-23a/24-2/27a cluster via the regulation of c-MYC, providing the potential for the miR-23a/24-2/27a cluster to be used as biomarker in the diagnosis and/or treatment of breast cancer.

DOI10.1002/anie.201302825
Alternate JournalJ. Biol. Chem.