MicroRNA-297b-5p/3p target Mllt3/Af9 to suppress lymphoma cell proliferation, migration and invasion in vitro and tumor growth in nude mice

Abstract

Mllt3/Af9 is a proto-oncogene capable of deregulating the expression of genes critical for leukemia. However, the regulation of its expression remains incompletely elucidated. Herein, we show that the microRNAs miR-297b-5p/3p are capable of regulating Mllt3/Af9 expression negatively by binding to its 3’-untranslated region. Overexpression of miR-297b-5p/3p also led to altered expression of p27^Kip1 and proliferating cell nuclear antigen, abnormal cell cycle arrest, decreased cell proliferation, migration and invasion in vitro in cell cultures, and suppressed xenograft tumor growth in vivo in the nude mouse. These data demonstrate that miR-297b-5p/3p and Mllt3/Af9 might be critical regulators of lymphoma cell proliferation or carcinogenesis. Together our findings suggest that miR-297b-5p/3p might be useful molecular targets for diagnosis or treatment of cancers associated with abnormal expression of Mllt3/Af9.

Keywords::

• miR-297b-5p/3p
• Mllt3/Af9
• lymphoma
• PCNA
• p27^Kip1

Acknowledgements

This work was supported in part by grants from the National Science Foundation of China (#30970649), the 973 Program of China (#2009CB941601), the Fujian Provincial Department of Science and Technology (#2010L0002) and the 111 Project of Education of China (#B06016).

Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.