Bioinformatics analysis to introduce novel long non-coding RNAs involved in tamoxifen resistance in breast cancer cells

Background and Aim: Breast cancer is the second leading cause of cancer death among women, and large number of new cases are reported each year. Many of patients are respond to Tamoxifen treatment but some of them are resistant or resistance to Tamoxifen may occur after utilize of the drug due to a variety of mechanisms, including error in DNA repair, dysregulation of genes expression and epigenetic processes. Presently, Tamoxifen resistance is a serious matter in endocrine therapy context for breast cancer patients. Numerous studies have proven the role of long non-coding RNAs in controlling and regulating drug resistance pathways. There have been many reports lncRNAs being associated with different types of cancer that makes them interesting, they are non-protein coding transcripts more than ۲۰۰ nucleotides length and have the potential to interact directly with certain areas of chromatin, some proteins and other non-coding RNAs. In this article, we're going to evaluate the most important effect of drug resistance-related lncRNA expression changes obtained by bioinformatics analysis and library studies on tamoxifen-resistant breast cancer cell lines.Methods: We downloaded the sequence data of human lncRNAs from the lncipedia database (http://www.lncipedia.org/), using several online databases, including Oncomine, PrognoScan, bc-GenExMiner, therefore lncRNAs that we proposed they are associated with tamoxifen resistance in breast cancer were examined and validated in Gene Expression Omnibus (GEO) (We could obtain data from these GASEs: GSE۵۸۴۰, GSE۲۱۶۵۳, GSE۱۹۶۱۵, GSE۲۰۶۸۵) and The Cancer Genome Atlas (TCGA), respectively.Results: Here, using bioinformatics analysis and RNA-seq data available with library research, online resources and articles, we investigate the alteration in expression of lncRNAs that demonstrate significant altered expression (logFc> ۱ and p-value <۰.۰۵) in Tamoxifen-resistant cell groups against sensitivities (MCF۷, DMSO ۴hrs treated / OHT resistant MCF۷, DMSO ۴hrs treated) finally, we were able to introduce new lncRNAs (such as LOC۱۰۱۹۲۷۰۶۹, LOC۱۰۱۹۲۷۸۵۱, LOC۱۰۱۹۲۷۸۰۹, LOC۱۰۰۵۰۶۶۹۱, LOC۱۰۱۹۲۹۷۱۸, LOC۱۰۲۵۴۶۲۹۹)Conclusion: Together, our studies indicate that mentioned lncRNAs may play a role in breast cancer tamoxifen resistance pathogenesis, suggested that alterations in expression of these long non-coding RNAs obtained by this statistical study could/may modulate the effect of drug resistance in patients or, by eliminating it, sensitize cells to Tamoxifen and may interact with other multidrug resistance factors in cultured cells like MDR۱/Pgp, MRP۱, and BRCP. In conclusion these results could beuseful for clinical aspects (may be a predictive biomarker) particularly in personalized medicine, however future research is required to validate our findings.

Keywords:

breast cancer , lncRNA , drug resistance , Tamoxifen