Analysis of miRNA expression profile induced by short term starvation in breast cancer cells treated with doxorubicin

Abstract

Recent studies showed that dietary approaches restricting food intake can be helpful to hinder tumor progression. To date, the molecular mechanisms are unclear and a key role seems to be exerted by nutrient-related signaling pathways. Since several evidences showed that non-coding small RNAs, including microRNAs, are correlated to cancer progression and antiblastic treatment response, our work aims to study their involvement in a triple negative breast cancer (TNBC) cell line treated with doxorubicin under Short Term Starvation (STS) condition. Human TNBC cell line MDA-MB-231 and healthy breast cell line MCF10A were treated with 1 μM doxorubicin for 24 h under STS condition for 48 h and miRNA expression profiles were analyzed using Taqman® Low Density Array A human microRNA microfluidic cards. In addition, the expression of specific mRNAs and miRNAs differentially expressed under STS was analyzed using Real-time PCR analyses. MiRNA expression profile analysis in MDA-MB-231 and MCF10A cells treated with doxorubicin under STS for 48 h could explain the molecular mechanisms underlying anticancer effects associated to STS. Among deregulated miRNAs, a subset, including miR-15b, miR-23a, miR-26a, miR-29a, miR-106b, miR-128, miR-149, miR-181a, miR- 192, miR-193b, miR-195, miR-324-3p and miR-494, has been shown to be involved in pathways related to drug sensitivity/resistance. The obtained data from our study suggest a potential involvement of some miRNAs in molecular pathways mediating the anticancer effects of STS in doxorubicin-treated breast cancer cells. Preliminary results seem to be encouraging and, in future, could allow the discovery of new potential targets useful for the development of new therapeutic approaches.