Bioinformatics analysis of differential expression Long non-coding RNA HOTAIR and related high targeting score miRNAs as diagnostic biomarkers in Tamoxifen-resistant breast cancer cells

Bioinformatics analysis of differential expression Long non-coding RNA HOTAIR and related high targeting score miRNAs as diagnostic biomarkers in Tamoxifen-resistant breast cancer cells
Foruzan Moradi,^1,* Majid Sadeghizadeh,²
1. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
2. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
Introduction: Breast cancer is a disease in which cells in the breast grow out of control. Tamoxifen (Tam) is a central component of the treatment of estrogen receptor positive (ER+) breast cancer as a partial agonist of ER. It has been clinically used for the last 30 years to successfully treat ER+ breast cancer. The most challenging issue with Tam use is the development of resistance in an initially responsive breast tumor. A group of non-coding RNAs are involved in the resistance of breast cancer cells to Tam. However, only a few of these non-coding RNAs have been clinically suggested as biomarkers for Tam resistance. Therefore, the search for non-coding RNAs in the blood of people with breast cancer treated with Tam can be suggested as a prognostic biomarker for the management of Tam resistance so that these patients can use another drug for treatment.
Methods: We compared the transcriptomes of Tam-sensitive and Tam-resistant MCF-7 breast cancer cells for identification of genes involved in the development of Tam resistance by using bioinformatics analysis and RNA seq data from GEO: GSE111151 number (Hultsch S et al., 2018). Important miRNAs (with high targeting score) that associated with HOTAIR RNA were searched through miRDB, StareBase, DIANA and miRcode tools.
Results: We found up-regulated expression of long non-coding RNA HOTAIR and negative expression relationship between hsa-miR-326, hsa-miR-4677-3p, hsa-miR-330-5p and hsa-miR-1277-5p RNAs with HOTAIR RNA in Tam-resistant cells.
Conclusion: An increase in HOTAIR RNA expression levels and a decrease in mir-196a-5p and hsa-miR-326, hsa-miR-4677-3p, hsa-miR-330-5p and hsa-miR-1277-5p RNAs expression levels in the blood samples of people treated with Tam, can be find as diagnostic biomarkers that the drug used for these patients should be changed because the patient cancer cells is becoming more resistant. It is hoped that future studies report more diagnostic biomarkers in resistant breast cancer patients.
Keywords: Tamoxifen-resistant, Breast cancer, Non-coding RNAs, Diagnostic biomarkers, Bioinformatics analysis.