Identification of Long Noncoding RNAs That Exert Transcriptional Regulation by Forming RNA–DNA Triplexes in Prostate Cancer

Abstract

Long noncoding RNAs (lncRNAs) are involved in transcriptional regulation, and their deregulation is associated with the development of various human cancers, including prostate cancer (PCa). However, their underlying mechanisms remain unclear. In this study, lncRNAs that interact with DNA and regulate mRNA transcription in PCa were screened and identified to promote PCa development. First, 4195 protein-coding genes (PCGs, mRNAs) were obtained from the The Cancer Genome Atlas (TCGA) database, in which 1148 lncRNAs were differentially expressed in PCa. Then, 44,270 pairs of co-expression relationships were calculated between 612 lncRNAs and 2742 mRNAs, of which 42,596 (96%) were positively correlated. Among the 612 lncRNAs, 392 had the potential to interact with the promoter region to form DNA:DNA:RNA triplexes, from which lncRNA AD000684.2(AC002128.1) was selected for further validation. AC002128.1 was highly expressed in PCa. Furthermore, AD000684.2 positively regulated the expression of the correlated genes. In addition, AD000684.2 formed RNA–DNA triplexes with the promoter region of the regulated genes. Functional assays also demonstrated that lncRNA AD000684.2 promotes cell proliferation and motility, as well as inhibits apoptosis, in PCa cell lines. The results suggest that AD000684.2 could positively regulate the transcription of target genes via triplex structures and serve as a candidate prognostic biomarker and target for new therapies in human PCa.

Non–Coding RNA Performs Its Biological Function by Interacting with Macromolecules

“…Secondly, the RNA-DNA triplex structure can recruit transcription factors or epigenetic modulators, thereby influencing gene transcription in both directions. Two independent studies have shown that the vast majority of lncRNAs positively regulate gene expression through RNA-DNA triplexes, suggesting that the first mode of regulation is more predominant [3,5].…”

Autophagy-related lncRNAs in tumor progression and drug resistance: A double-edged sword

“…vi) lncRNAs can interact with genomic DNA to form triplexes thereby regulating target gene transcription. 13 , 14 , 15 , 16 …”