Exp Mol Med.  2010 Nov;42(11):759-767. 10.3858/emm.2010.42.11.077.

Suppression of Aurora-A oncogenic potential by c-Myc downregulation

• Yang S
• He S
• Zhou X
• Liu M
• Zhu H
• Wang Y
• Zhang W
• Yan S
• Quan L
• Bai J
• Xu N

• KMID: 994399
• DOI: http://doi.org/10.3858/emm.2010.42.11.077

Abstract

The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrations. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophageal cancer cells. Taken together, our results suggest an important role for c-Myc in mediating the oncogenic activity of Aurora-A, which may in turn allow for future targeting of c-Myc as a potential therapeutic strategy for tumors with Aurora-A overexpression.

Keyword

aurora kinase; neoplasms; proto-oncogene proteins c-myc; RNA interference

MeSH Terms

Cell Line, Transformed
Cell Proliferation/drug effects
Cell Transformation, Neoplastic/drug effects/genetics
Centro
Chromo
Cisplatin/pharmacology
Down-Regulation
E
Gene Expression Regulation, Neoplastic/drug effects
Humans
Protein-Serine-Threonine Kinases/genetics/*metabolism
Proto-Oncogene Proteins c-myc/genetics/*metabolism
RNA, Small Interfering/genetics
Transcriptional Activation
Transgenes/genetics