Title : Bioinformatics and genomic approaches for assessing gene fusion process in MCF7 breast cancer cell models under early estradiol stimulation for assessing estrogen receptor ? (Er?) tumor suppressor activity
Abstract:
Cancers are genetic and epigenetic diseases in which cells divide and grow in uncontrolled ways due to mutations or molecular alterations. Gene fusion phenomena is recurrent in cancer cells. One of the most common cancers is breast cancer, representing worldwide public health concern. Several studies showed the involvement of estrogens and estrogen nuclear receptors in monitoring breast cancer. Indeed, integration between genomic and bioinformatics tools strongly contribute in improving cancer molecular biology interpretation and comprehension. Herein, we performed a transcriptomic analysis aiming to assess gene fusion events in MCF7 breast cancer (BC) models that expressed estrogen nuclear receptors α/β under early (2h) estradiol (E2) stimulation. We aligned genomic reads sequences of that BC model on the GRCh38 human genome, by using RNA-STAR. Next, we executed gene fusion calling via star-fusion package. Results showed a non-significant variability regarding gene fusion happening events between estradiol-stimulated (MCF7E) and non-stimulated (MCF7noE) MCF7 BC cells lines (p>0.05). Common detected genes fusions between analyzed BC models result to be biomarkers of several cancers including BC, and were characterized by the intra-chromosomic interactions. Findings revealed five (5) gene fusion events specific to BC cells lines non-stimulated (MCF7noE), and recognized as BC biomarkers. Results exhibited estrogen nuclear receptor beta (Erβ) as inhibiting the expression of these BC biomarkers in MCF7 BC cells lines under estradiol stimulation (MCF7E). In conclusion, even if early estrogen hormone stimulation by inducing nuclear Erβ has non-significant impact on gene fusion variability between MCF7noE and MCF7E BC cell line models by contrast to the alternative splicing event, present study highlighted onco-suppressor activity of Erβ in breast cancer.
Keyword: MCF7 Breast Cancer, Gene Fusion, Estradiol (E2), Estrogen nuclear receptor α and β (Erα and Erβ).
