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Kidney Week

Abstract: TH-PO743

Novel Diagnostic and Therapeutic Approaches for Kidney Diseases: Potential Applications of Noncoding RNAs Associated with Regulation of NOTCH2 and TP53

Session Information

Category: Genetic Diseases of the Kidney

  • 1002 Genetic Diseases of the Kidney: Non-Cystic

Authors

  • Al-Obaide, Mohammed A., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
  • Vasylyeva, Tetyana L., Texas Tech University Health Sciences Center, Amarillo, Texas, United States
Background

The NOTCH2 and TP53 genes are linked to many diseases including kidney diseases. In humans NOTCH2 associated with kidney developmental abnormalities and Alagille Syndrome. In addition to the known function of TP53 in limiting cell proliferation, TP53 involved in regulation of self-renewal and maintenance of the nephron progenitor pool. Previous studies showed excessive expression linkup NOTCH2 and TP53 to kidney diseases. We hypothesized that long noncoding RNA (lncRNA) which are tissue-specific regulators of gene expression are involved in cross-talk for tight control of expression of genes associated with kidney diseases, for example, the NOTCH2 and TP53. The genomic regions of the two genes host characterized and uncharacterized lncRNA. We aimed to investigate the potential interaction and cross-talk between the WRAP53 WD repeat containing antisense to TP53 and the uncharacterized lncRNA genes convergently or divergently configured to the protein-coding gene NOTCH2 in the regulation of both genes.

Methods

The search for unreported miRNA sequences in the WRAP53 WD repeat containing antisense to TP53 and predicted uncharacterized lncRNA LOC105378939, LOC111776218, LOC101929178 and LOC105378940 ncRNAs loci analyzed by the miRBase search tool. The microRNA recognition elements (MRE) in the NOTCH2 and TP53 mRNAs, identified by RNA22 v2 microRNA target detection tool. The miR binds to the target MRE.

Results

The lncRNAs loci are the source of various types of miRNAs. The analysis of the WRAP53 WD repeat containing antisense to TP53 and LOC105378939, LOC111776218, LOC101929178, and LOC105378940 detected several types of miRs. The discovered miRs bind to the target MRE of the mRNAs of the NOTCH2 and TP53. The miRs from WRAP53 WD repeat containing antisense to TP53 bind the MRE targets of NOTCH2. The miR sequences are comparable but not similar to the human (Homo sapiens) hsa-miR, for example, hsa-miR-6743-3p, hsa-miR-6510-5p, hsa-miR-1285-3p, and hsa-miR-519b-3p.

Conclusion


The detected miRNAs from the investigated lncRNAs may provide novel approaches to delineate the complex mechanisms associated with NOTCH2 and TP53 in kidney diseases. The lncRNAs can act as diagnostic biomarkers and suggest therapeutic opportunities for the treatment of kidney diseases.