Assessment of correlation between Trastuzumab resistance and miR-885-3p relative expression in the BT-474 Human Breast Cancer Cell Line

Document Type: Original Article

Authors

1 Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran

2 Cellular and Molecular Research Center, Birjand University of Medical Sciences , Birjnad. Iran

Abstract

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-885-3p in HER2 positive breast cancer chemoresistance. Trastuzumab-resistant BT-474 cells were generated by in vitro culture of BT-474 cells continuously in the presence of trastuzumab about 9 months. The relative expression of miR-885-3p to U6 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-474 breast cancer cells were resistant to this drug under long-term culturing with trastuzumab (p < 0.05). MiR-885-3p expression was also significantly downregulated in trastuzumab-resistant cells in comparison with the parent cells (p < 0.05).:  As the relative expression of candidate microRNAs was statistically different in trastuzumab-resistant and sensitive cells, we hypothesize that miR-885-3p downregulation as a possible mechanism of trastuzumab resistance.

Keywords


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