lncRNA HCG11 regulates the expression level of SP1 as a potential prognostic biomarker of BC during the polymerase II transcription process in an HCG11/miR-106a-3p/SP1 axis: integrated bioinformatics and experimental investigation

Background Breast cancer (BC), one of the ten most common diseases in the world, is a common malignant tumor that forms from the women's breast epithelial tissue. According to Cancer Statistics 2020, over 1.7 million new cancer cases are detected yearly. In this research, we aimed to evaluate the expression level and interaction network of the SP1 gene, and it’s regulatory non-coding RNAs in the BC samples. Method High-throughput microarray data analysis was performed on GSE42568 (27 control and 31 tumors) to find the up and down-regulated genes in BC patients. Reactome performed pathway enrichment analysis. Enrichr performed gene ontology analysis. Comprehensive protein-protein (STRING), miRNA-mRNA (miRWalk), and miRNA-lncRNA (lncBase 3) was performed to find the RNA regulatory network of SP1. Cytoscape performed visualization of RNA network. The qRT-PCR experiment was performed to validate the changes in the expression level of SP1 and related non-coding RNAs in the BC samples. Results Microarray analysis revealed that SP1 has a significantly low expression in the BC samples. lncRNA HCG11 regulates SP1 in direct interaction and ceRNA axis (binding affinity to hsa-miR-106a-3p). hsa-miR-106a-3p regulates the expression level of SP1 during regulating the transcriptional activity of the SMAD2/SMAD3:SMAD4 heterotrimer process. qRT-PCR experiment revealed that SP1 (logFC: -4.174, p-value: 0.0007) and lncRNA HCG11 (logFC: -4.223, p-value: 0.0003) have significant low-expression in the BC samples. ROC analysis revealed that SP1 (AUC: 0.7312, p-value: 0.07074) HCG11 (logFC: 0.7312, p-value: 0.07505) could be the two potential diagnostic biomarkers of BC. Conclusion SP1 and lncRNA HCG11 have significantly low expression in the BC samples as the two potential diagnostic biomarkers. Has-miR-106a-3p regulates the expression level of HCG11 and SP1 in a ceRNA axis. This axis might be a novel regulatory factor in response to the hydroperoxide process.