Interactions of piRNAs with the mRNA of Candidate Genes in Esophageal Squamous Cell Carcinoma

Curr Issues Mol Biol. 2023 Jul 23;45(7):6140-6153. doi: 10.3390/cimb45070387.

Abstract

Recently, a database of human piRNAs (piwi-interacting RNAs) was created, which allows the study of the binding of many piRNAs to the mRNAs of genes involved in many diseases, including cancer. In the present work, we identified the piRNAs that can interact with candidate esophageal squamous cell carcinoma (ESCC) genes. The binding of 480 thousand piRNAs with the mRNAs of 66 candidate ESCC genes was studied. Bioinformatic studies found that piRNAs bind only to the mRNAs of nine candidate genes: AURKA, BMP7, GCOM1, ERCC1, MTHFR, SASH1, SIX4, SULT1A1, and TP53. It has been shown that piRNAs can bind to mRNA by overlapping nucleotide sequences in limited 3'UTR and 5'UTR regions called clusters of binding sites (BSs). The existence of clusters of piRNA BSs significantly reduces the proportion of the nucleotide sequences of these sites in the mRNA of target genes. Competition between piRNAs occurs for binding to the mRNA of target genes. Individual piRNAs and groups of piRNAs that have separate BSs and clusters of BSs in the mRNAs of two or more candidate genes have been identified in the mRNAs of these genes. This organization of piRNAs BSs indicates the interdependence of the expression of candidate genes through piRNAs. Significant differences in the ability of genes to interact with piRNAs prevent the side effects of piRNAs on genes with a lack of the ability to bind such piRNAs. Individual piRNAs and sets of piRNAs are proposed and recommended for the diagnosis and therapy of ESCC.

Keywords: diagnosis; esophageal squamous cell carcinoma; gene; mRNA; piRNA.