Down-regulation of PEAR1 and its regulatory factor, LINC00271, as the potential novel tumor suppressors in breast cancer: bioinformatics and experimental approach

Abstract

Abstract In addition to coding region, non-coding genes can also be involved in the development of cancer cells. Therefore, the present study aimed to study the expression level of the coding gene PEAR1 and non-coding gene LINC00271 in breast tumors. Using bioinformatics approaches, the DE genes and miRNAs in breast cancer tissue were extracted from datasets. MiRNA-target regulatory network visualization in Cytoscape along with applying Cytohubba lead to identifying hub-miRNAs and their targets in breast tumors. Functional enrichment analysis was done using MIEAA database. The co_lncRNA and lncBASE databases were utilized to find effective lncRNA. Verifying the PEAR1 and LINC00271 expression in breast tumor and adjacent healthy cells was carried by Real-Time PCR assay. Analysis of array-based non-coding expression profile resulted in 96 significant DE miRNAs which 15 out of them were collected as hub-miRNAs due to the number of their target genes. 4 common genes were identified between targets of hub-miRNAs and DE genes in breast tumors; among them, PEAR1 was considered as novel DE gene which also was one of the targets of upregulated hub-miRNAs, hsa-miR-34a-5p. LINC00271 was selected as correlated lncRNA with PEAR1 and hsa-miR-34a-5p. qRT-PCR results revealed that the expression level of both PEAR1 and LINC00271 were significantly down-regulated (Fold change PEAR1 = 0.00798/P-Value < 0.0001, Fold change LINC00271 = 0.09/P-Value = 0.0094) in breast tumors compared to controls. Due to a significant reduction in PEAR1 and LINC00271 expression and array-based reported, the association between these genetic factors can be considered as new molecular markers in the prognosis and metastasis of breast cancer.