Bioinformatics analysis of differential expression Long non-coding RNA MALAT۱ and related important miRNAs in Tamoxifen-resistant breast cancer cells

Background and Aim: Breast cancer is one of the most common cancers in women worldwide. Tamoxifen (Tam) has been used for many years to successfully treat ER+ breast cancer. However, adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one third of patients treated with Tam within ۵ years of therapy. One of the mechanisms leading to patients' resistance to Tam is the aberrant expression of non-coding RNAs (miRNAs and long non-coding RNAs). Therefore, searching for non-coding RNAs for the management of tamoxifen resistance is very valuable.Methods: Using RNA seq data from GEO: GSE۱۱۱۱۵۱ number (Hultsch S et al., ۲۰۱۸), we compared the transcriptomes of Tam-sensitive and Tam-resistant MCF-۷ breast cancer cells for identification of genes involved in the development of Tam resistance. Important miRNAs (with high targeting score) that associated with Long non-coding RNAs were searched through miRDB, StareBase, DIANA and miRcode tools.Results: We identified up-regulated expression of long non-coding RNA MALAT۱ in Tam-resistant cells. Furthermore, we found the negative expression relationship between hsa-miR-۳۲۶, hsa-miR-۲۶a-۵p, hsa-miR-۲۰۶ and hsa-miR-۲۰۵-۵p with the long non-coding RNA MALAT۱.Conclusion: Aberrant expression of non-coding RNAs is one of the mechanisms leading to patients' resistance to Tam. Overexpression of selected miRNAs, hsa-miR-۳۲۶, hsa-miR-۲۶a-۵p, hsa-miR-۲۰۶ and hsa-miR-۲۰۵-۵p which down-regulated or suppression of their target, MALAT۱ which is up-regulated in Tam-resistant cells may improve Tam-resistant breast cancer cells’ response to Tam. It can be a new strategy for the sensitivity of Tam-resistant cells.

Keywords:

Tamoxifen-resistant , Breast cancer , Non-coding RNAs