Comprehensive transcriptomic analysis reveals a relation between expression alteration of transcribed ultraconserved regions (T-UCR) and hypoxia

Introduction & Objectives: The transcribed ultraconserved regions (T-UCRs) are noncoding RNAs that are nearly 100% conserved between the genome of three species:human, rat and mouse. Selective conservation of these sequences during evolution suggests that these areas are important and necessary elements for proper cell function. UCRs are often located in the fragile sites and cancer-associated genomic regions. Therefore, it is suggested that these regions may be candidate genes for cancer susceptibility. Hypoxia has been recognized as one of the fundamentally important features of many malignancies and plays a critical role in many aspects of cancer biology, including cell proliferation, angiogenesis, immunosurveillance, metabolism, and tumor invasion and metastasis. Here, we aim to investigate the expression profile alterations and potential function of all T-UCRs under hypoxic conditions. Materials & Methods: RNA-seq raw data were downloaded from Array-Express database (E-MTAB-2580). The data were then aligned to the human genome reference (hg19) by using HISAT2, then htseq-count was utilized to quantitate the number of reads mapping into each T-UCR. Differential expression analysis was then performed using DESeq2 to identify deregulation of T-UCRs. The fold change (FC) values of individual T-UCR levels were calculated and differentially expressed T-UCRs with |log2(fold change)|> 1 and adjusted P-value < 0.05 were considered to be statistically significant. Results: In the present study, we compared RNA sequencing data set of 12 human embryonic kidney (HEK293) cells exposed to normoxia compared to hypoxia conditions for 24 hours. Using the cut-off criteria, we identified T-UCRs that were differentially expressed in the hypoxia and then using PANTHER ontological analysis, we classified hypoxia-induced and repressed genes according to the gene ontology. Conclusion: This type of studies increases our understanding of the complex mechanisms of hypoxia mediated by T-UCRs and will aid in identifying potential candidates for pharmacological intervention of cancer.