Genome-wide profiling of dysregulated piRNAs and their target genes implicated in oncogenicity of tongue squamous cell carcinoma

Abstract

PIWI-interacting RNAs (piRNAs) are single-stranded, 23–36 nucleotide long RNAs that regulate gene expression in the germline but are also detected in some cancers. However, there are no reports yet on piRNA expression in tongue squamous cell carcinoma (TSCC), the most common oral cancer (80–90% percent of all oral cancers). We performed small RNA and whole transcriptome sequencing in H357 tongue cancer and HOK cells (GEO database accession numbers: GSE196674 and GSE196688). We also examined nine published sets of gene expression array data of TSCC tissues from the GEO database to decode piRNAs and their putative targets that may be involved in tumorigenesis. We identified a pool of 16,058 and 25,677 piRNAs in H357 and HOK, respectively, among which 406 are differentially expressed. We also found that 2094 protein-coding genes are differentially expressed in either TSCC tissues or cell lines. We performed target predictions for these piRNAs, pathway and disease function (DF) analyses, as well as qRT-PCR validation of piRNA-target pairs. These experiments revealed one up-regulated (FDFT1) and four down-regulated (OGA, BDH1, TAT, HYAL4) target genes that are enriched in 11 canonical pathways (CPs), with postulated roles in the initiation and progression of TSCC. Downregulation of piR-33422 is predicted to upregulate the FDFT1 gene, which encodes a mevalonate/cholesterol-pathway related farnesyl-diphosphate farnesyltransferase. The FDFT1 appears to be involved in the largest number of oncogenesis-related processes and is interacting with statins, which is a classical cancer drug. This study provides the first evidence of the piRNome of TSCC, which could be investigated further to decode piRNA-mediated gene regulations in malignancy and potential drug targets, such as FDFT1.