The profiles of miR-4510 expression level in breast cancer

Abstract

AbstractMicroRNA that is abnormally produced in breast cells can disrupt biological processes, which can lead to cancer. This study aims to screen differentially expressed genes (DEGs) and ncRNAs (DEncRNAs) in the formalin-fixed paraffin-embedded (FFPE) tissues of breast cancer (BC) as compared with the normal adjacent tissues (NAT), and identify miR-4510 as a novel biomarker of BC. This study looked at differentially expressed genes (DEGs) using MACE-Seq and differentially expressed ncRNAs (DEncRNAs) using the small RNA-Seq. Real-time qPCR was used to determine the level of expression of miR-4510. In this study, MACE-Seq results showed that 26,795 genes, with a p-value < 0.05, were differentially expressed in BC paraffin tissues as compared with NAT. Small RNA-Seq results revealed that 1326 ncRNAs, with a p-value < 0.05, were differentially expressed. We confirmed that miR-4510 was significantly down-expressed (p-value = 0.001) by qRT-PCR in the paraffin tissue of 120 BC patients. Based on eleven computational prediction programs, TP53, TP53INP1, MMP11, and COL1A1 for the miR-4510 were identified as miR-4510 targets. The MACE-seq result showed that the gene of TP53 (p-value = 0.001) and TP53INP1 (p-value = 0.02) was significantly down-regulated, but the gene of MMP11 (p-value = 0.004) and COL1A1 (p-value = 0.0001) was significantly over-expressed in 20 paired specimens of the BC and NAT. We discovered that a single SNP inside the miR-4510 binding site occurred only in BC, in which Guanine (G) changed into Adenine (A). Two SNPs outside the miR-4510 binding site occurred, and Guanine (G) in both BC and NAT was changed into Thymine (T), as compared to the reference sequence (RefSeq). Overall, our results suggested that miR-4510 functions as a tumor suppressor in the BC. Mir-4510 may act as a tumor suppressor, however additional experimental data is needed to corroborate these assumptions and can be exploited as a biomarker for BC.