Assessment of correlation between Trastuzumab resistance and miR-۸۸۵-۳p relative expression in the BT-۴۷۴ Human Breast Cancer Cell Line

Trastuzumab has been applied widely in the treatment of breast cancer. The majority of initial responders display disease progression again within one year. Regardless of the high resistance rate, the molecular mechanisms affected this disease are not well understood. MicroRNAs are small, non-coding RNA molecules that involved in gene regulation. There is evidence that promotes miRNAs as potential candidates to mediate therapeutic actions by targeting genes involved in drug response. The purpose of this study is to evaluate miR-۸۸۵-۳p in HER۲ positive breast cancer chemoresistance. Trastuzumab-resistant BT-۴۷۴ cells were generated by in vitro culture of BT-۴۷۴ cells continuously in the presence of trastuzumab about ۹ months. The relative expression of miR-۸۸۵-۳p to U۶ RNA was evaluated in trastuzumab-resistant and sensitive cells using Relative Real-Time PCR. The Mann-Whitney test is used to compare the differences between the two groups. The MTT assay showed that BT-۴۷۴ breast cancer cells were resistant to this drug under long-term culturing with trastuzumab (p < ۰.۰۵). MiR-۸۸۵-۳p expression was also significantly downregulated in trastuzumab-resistant cells in comparison with the parent cells (p < ۰.۰۵).:  As the relative expression of candidate microRNAs was statistically different in trastuzumab-resistant and sensitive cells, we hypothesize that miR-۸۸۵-۳p downregulation as a possible mechanism of trastuzumab resistance.

Keywords:

Breast cancer , HER۲ , Trastuzumab , Resistance , miR-۸۸۵-۳p