Researchers at Moffitt Cancer Center have discovered that the micro ribonucleic acid miR-214 plays a critical role in regulating ovarian cancer stem cell properties. This knowledge, said the researchers, could pave the way for a therapeutic target for ovarian cancer.
The study appears in a recent issue of the The Journal of Biological Chemistry.
According to the study's lead author, Jin Q. Cheng, Ph.D., M.D., senior member of the Molecular Oncology Department and Molecular Oncology and Drug Discovery Program at Moffitt, certain miRNAs can cause therapeutic resistance and cancer metastasis by regulating multiple gene targets. Previous work has shown that one microRNA -- miR-214 -- is elevated in cancer. In ovarian cancer, up-regulated miR-214 has been associated with late-stage and high-grade tumors. In past research, miR-214 has also been associated with resistance to the chemotherapy drug cisplatin, but the role played by miR-214 in cancer stem cells had not been determined.
"Evidence suggests that cancer stem cells are responsible for cancer initiation, progression, metastasis, chemoresistance and relapse," Cheng said. "Data are emerging to support the role of both miRNAs and transcription factor p53 in cancer stem cell regulation."
Their current study found that miR-214 regulates ovarian cancer stem cell properties by direct repression of p53, which led to induction of a stem cell transcription factor (Nanog). The researchers demonstrated that p53 mediated miR-214-induced Nanog in ovarian cancer stem cells and also induced chemoresistance.
"It is plausible that miR-214 has an important influence on stem cells through its capacity to modulate p53," explained Cheng. "Our study demonstrates direct evidence that miR-214 plays a critical role in maintaining ovarian cancer stem cells."
Given that knowledge, the researchers concluded that miR-214 is a potential therapeutic target for treating ovarian cancer.
- C.-X. Xu, M. Xu, L. Tan, H. Yang, J. Permuth-Wey, P. A. Kruk, R. M. Wenham, S. V. Nicosia, J. M. Lancaster, T. A. Sellers, J. Q. Cheng. MiR-214 regulates ovarian cancer cell stemness by targeting p53/nanog. Journal of Biological Chemistry, 2012; DOI: 10.1074/jbc.M112.374611
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