Title:Delta Np63 alpha – Responsive microRNA Modulate the Expression of Metabolic Enzymes
Volume: 16
Issue: 9
Author(s): Edward A. Ratovitski
Affiliation:
Keywords:
Cancer, chemoresistance, cisplatin, microRNA, metabolism, tumor protein p63.
Abstract: MicroRNAs, whose transcription is regulated by members of the tumor protein p53 family,
modulate the expression of numerous metabolic enzymes, significantly altering tumor cell response to
chemotherapeutic treatments. The role for ΔNp63α-regulated microRNAs in regulation of cell cycle
arrest, apoptosis and autophagy in squamous cell carcinoma (SCC) cells upon cisplatin exposure has
been reported. The current study indicated that the selected microRNA targets differentially regulated
by ΔNp63α in cisplatin-sensitive and cisplatin-resistant SCC cells could alter the expression of a few
metabolic enzymes, thereby potentially contributing to the metabolic changes in SCC cells upon cisplatin
exposure. Finally, the modulation of specific targets (e.g., SREBF2, AKT2, G6PD, CPS1, FADS1, and ETNK1) using
a combination of microRNA mimics and siRNA silencing has shown that a suppression of these metabolic factors/ enzymes
could confer a sensitivity of SCC cells to cisplatin. Thus, the Δ Np63α-regulated microRNAs were found to regulate
the levels of several metabolic factors and enzymes, thereby potentially contributing to the response of larynx and
tongue-derived SCC cells to platinum chemotherapy.
