Identification of LncRNA expression signatures for triple_negative breast cancer by bioinformatics analysis
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sara soltani tehrani,1 melika golshayan,2,*
1. Undergraduate student of Cellular and Molecular Biology, Department of Biological Sciences and Technologies, Faculty of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran
2. Undergraduate student of Cellular and Molecular Biology, Department of Biological Sciences and Technologies, Faculty of Materials Engineering, Najafabad Branch, Islamic Azad University, Najafabad, Iran
- Introduction: Triple-negative breast cancer (TNBC) is a typical molecular subtype of breast cancer that lacks the expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) and accounts for 10-20% of all types of breast cancer (1,2). Currently, no specific targeted therapy is available for TNBC (3). Therefore, it is crucial to identify potential biomarkers and novel therapeutic targets to develop a more efficient treatment. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play a vital role in various biological processes, including genetic transcription, chromosome modification, cell differentiation, and migration (4-6).lncRNA breast cancer antiestrogen resistance 4 (BCAR4) produces a spliced long non-coding RNA (lncRNA) that has been implicated in breast cancer metastasis. It was originally identified in a screen for genes responsible for developing resistance to antiestrogens in breast cancer cells. It is thought that the release of CCL21 enables this lncRNA to bind to the SNIP1 and PNUTS transcription factors, thereby activating a non-canonical GLI-dependent hedgehog signaling pathway that promotes cancer cell migration and invasion(7). The present study searched published microarray and sequencing data in the Gene Expression Omnibus (GEO). A sample size of patients with TNBC to identify candidate RNA signatures in TNBC that BCAR4 involves TNBC‑specific RNAs. These integrated analyses aimed to detect novel lncRNA/miRNA/mRNA biomarkers of TNBC and reveal the underlying molecular regulatory mechanisms of TNBC pathogenesis and progression.
- Methods: Focusing on bioinformatics aspects, Data mining and Microarray datasets, including GSE38959 (8), GSE61723 (9), GSE61724 (9), GSE76250 (10), and one dataset obtained by expression profiling via high-throughput sequencing, namely GSE58135 (11), were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) and the cancer genome atlas database. NCBI obtain some information about BC to determine the chromosomal profile of BCAR4 and target genes. The LncRNA and disease database helped find diseases associated with BCAR4 (BCAR4) expressed in 27% of primary breast tumors. Forced expression of BCAR4 in human ZR-75-1 and MCF7 breast cancer cells resulted in cell proliferation in the absence of estrogen and the presence of various antiestrogens. BCAR4 may be a good target for treating antiestrogen-resistant breast cancer). The Genomic Locations for BCAR4 Gene found in GENECARD, and Latest Assembly showed in chr16:11,808,312-11,828,905, and its expression levels in different organs ( both tumor and normal state ) evaluated in the GEPIA2 database.
- Results: RNA sequencing data analysis between patients with breast cancer and healthy individuals showed valuable results. The result of these studies was identified that about 29% of BC patients expressed BCAR4. Patients with high expression of BCAR4 had short progression-free survival (PFS), distant metastasis-free survival (MFS), and overall survival (OS). In addition, research on molecular mechanisms found that BCAR4 activated a noncanonical Hedgehog/GLI2 signal pathway and promoted cells migration [12]. As about 70% of BC patients are estrogen receptor-positive, antiestrogen therapy is considered an effective treatment. However, resistance has already been the main challenge for antiestrogen therapy. BCAR4 is one of the critical genes related to antiestrogen resistance [13]. It is found that overexpression of BCAR4 promoted BC cells growth through a non-estrogen-dependent pathway [13]. After overexpressing BCAR4, BC cells turned sensitive into resistant to antiestrogen [14].
- Conclusion: In this study, we found the critical gene ( BCAR4 ) that performs an oncogene role in Breast cancer. The high expression level of BCAR4 indicates a poor prognosis for BC patients that can be a candidate target for diagnostic, therapeutic, and preventive purposes.
- Keywords: Triple-negative breast cancer, lncRNAs, BCAR4, GEO database
