Identification of bidirectional promoters as the major source of gene expression regulation-associated non-coding RNAs in breast cancer: in silico
Identification of bidirectional promoters as the major source of gene expression regulation-associated non-coding RNAs in breast cancer: in silico
Mahboobeh Ramezani,1,*Fatemeh Shamsabadi,2
1. Department of Medical Genetics, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran. 2. Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Golestan University of Medical Sciences, Gorgan, Iran
Introduction: Identification of new potential biomarkers for early diagnosis and targeted therapy of breast cancer is demanded. In silico approaches improves our knowledge regarding to the cancer-associated genes.
We focused, in this survey, on the bidirectional promoter genes in breast cancer.
Methods: RNA-Seq data for solid tumor and primary of breast tissues and the adjacent normal tissues were retrieved from the Cancer Genome Database. The expressed genes more than 2 fold obtained by DESeq package in R software. To recognize the transcription factors the GeneCards resource was used.
Results: Three bidirectional genes were identified; of which the WT1 (4.793) and TYMS (2.02) were greatly transcribed while transcription of RNPC3 (-0.79) decreased with P adjusted value of <0.001. Interestingly, the same transcription level of coding genes was observed for WT1-As (4.79) and TYMSOS (2.2) antisense, as well as AC095032.1 lncRNA (-2.57). These protein coding genes locate on the chromosomes 11, 18, and 1. Thirty similar transcription factors (TFs) were identified in these bidirectional promoters by the GeneCards resource (P<0.001). Only E2F1 was up-regulated more than 2 fold. However, among the significantly changed TFs, HDAC1, RNF2, and HDAC2 were introduced as hub genes by Cytoscape. These TFs were involved in DNA damage, metabolism of proteins, p53, and Notch signaling pathways.
Conclusion: Bidirectional non-coding RNAs (ncRNAs) generally regulate the expression of their protein-coding counterparts through epigenetic modification and promoter targeting. It can therefore be assumed that these bidirectional non-coding genes with different expression may serve an important roles in breast cancer.
This finding has also important implications for developing tumor-specific targeting in cancer gene therapy
Keywords: Bidirectional promoter; breast cancer; WT1; TYMS; RNPC3.