Altered Expression Of Tumor-Suppressor And Oncogenic MicroRNAs May Predict Response To Paclitaxel Therapy In Breast Cancer

BARADARAN B. ^1,2 , ASGHARI F. ^1,2 , HAGHNAVAZ N. ^1,2 , SHANEBANDI D. ^1,2

Purpose: MicroRNAs (miRNAs) are small non-coding RNAs which have been interested in tumorigenesis and could play tumor-supressive or oncogenic roles, based on their target genes. In this study, expression of four tumor-suppressor and oncogenic microRNAs and their target genes in HER2-positive (BT-474 and SKBR-3) and HER2-negative (MCF-7 and MDA-MB-231) breast cancer cell lines was investigated before and after treatment with Paclitaxel. Methods: Expression level of miRNAs was investigated using quantitative real-time PCR. Results: Expression of both let-7a and miR-205 as tumor suppressors were significantly increased in HER2 over-expressing cell line BT-474 (26.4 fold, p=0.0009 and 7.2 fold, p=0.00013, respectively). In contrary, HER2 negative cell lines, MCF-7 and MDA-MB-231, showed significant decreased expression of both let-7a (30.3 fold, p<0.0001 and 13.5 fold, p<0.0001, respectively) and miR-205 (20 fold, and 18.1 fold, p<0.0001 respectively). Controversially, SKBR-3 revealed mild decreased expression of both let-7a (1.3 fold) and mir-205 (1.3 fold). For important oncomirs, expression level of both miR-21 and miR-203 were increased in HER2-positive cell lines BT-474 (17.66 fold, p=0.002 and 2.09 fold, p=0.06, respectively) and SKBR3 (2.42 fold, p=0.008 and 2.07 fold, p=0.0002, respectively). HER2-negative cell lines, MCF-7 and MDA-MB-231 showed decreased expression of both miR-21 (0.02 fold, and 0.3 fold, respectively) and miR-203 (0.09 fold, and 0.006 fold, respectively). Conclusions: Increased and decreased levels of tumor-suppressor miRNAs were more prominent than oncomirs in BT-474 HER2-positive cell line and HER2-negative cell lines, respectively. This could partially explain different response of HER2-positive and –negative and also better response of HER2-positive breast cancers to paclitaxel therapy. On the other hand, differential expression of miRNAs could be useful biomarkers for response to therapy. However, more studies with broad spectrum of cell lines and patient samples, and also for different miRNAs need for better conclusion.
Funding source: Immunology research center, Tabriz University of Medical Sciences