Identification of Key miRNAs Responsible for Bone Metastasis in Triple Negative Breast Cancer using BIoinformatic Approaches

Abstract

Triple Negative Breast Cancer stands for TNBC that indicates the lack of Estrogen Receptor [ER], Progesterone Receptor [PR] and Human Epidermal Growth Factor Receptor 2 [HER2]. In TNBC patients, the major cause of death is metastasis and its molecular mechanism is poorly understood till date with low survival rate globally. TNBC is highly hostile and it can be said that approximately 45-47% TNBC patients will have distant metastasis. The molecular mechanims for developing metastasis is unclear and also no biomarker for TNBC has been reported in order to help in the treatment modalities. Hence, it is important to identify the biomarkers for TNBCs as well as Metastasis. This study is targeted to identify the potential key miRNAs which are mainly responsible for bone metastasis in TNBC using bioinformatics approaches. Data including only Homo Sapiens species was extracted from GEO database. Amongst which, seven TNBC and three lymph node metastatic datasets were taken into consideration to derive significant p-values and fold change. Using GEO2R, groups were defined for samples of each dataset, thereafter, 1447 and 1255 unique miRNAs were acquired by generatingthe Venn diagram between TNBC and Metastasis respectively. Correspondingly, 186 common miRNAs were spotted during the construction of Venn diagram of all three metastasis datasets (GSE100453, GSE38167, GSE45498). These 186 obtained miRNAs were further analysed by setting a cut-off with p-value ≤ 0.05 or Fold change (FC) ±1. Later, three miRNAs (hsa-miR-542, hsa-miR-338, hsa-miR-136) were found to be unique which may be responsible for developing metastasis in TNBC. After undergoing literature search of all the three miRNAs, it was observed that they played role in Osteosarcoma, a malignant tumor of bone and thus survival analysis of those miRNAs was performed using Kaplan-Meier Plotter. miR-542-5p was discovered to have significant fold change in all the three datasets. miR-542- 5p targeting 1050 genes were detected using TargetScan. Gene interaction network was constructed with the help of Cytoscape. Furthermore, two genes, HDAC2 and SLC17A7 were found with significant P-value and expression values. Thus, it was concluded that hsa-miR- 542-5p might be responsible for the change in expression of both the genes. Moreover, we are trying to establish utility of miR-542-5p as an independent biomarker.