Transcriptional regulation of nuclear miRNAs in tumorigenesis (Review)

Abstract

MicroRNAs (miRNAs/miRs) are a type of endogenous non‑coding small RNA that regulates gene expression. miRNAs regulate gene expression at the post‑transcriptional level by targeting the 3'‑untranslated region (3'UTR) of cytoplasmic messenger RNAs (mRNAs). Recent research has confirmed the presence of mature miRNAs in the nucleus, which bind nascent RNA transcripts, gene promoter or enhancer regions, and regulate gene expression via epigenetic pathways. Some miRNAs have been shown to function as oncogenes or tumor suppressor genes by modulating molecular pathways involved in human cancers. Notably, a novel molecular mechanism underlying the dysregulation of miRNA expression in cancer has recently been discovered, indicating that miRNAs may be involved in tumorigenesis via a nuclear function that influences gene transcription and epigenetic states, elucidating their potential therapeutic implications. The present review article discusses the import of nuclear miRNAs, nucleus‑cytoplasm transport mechanisms and the nuclear functions of miRNAs in cancer. In addition, some software tools for predicting miRNA binding sites are also discussed. Nuclear miRNAs supplement miRNA regulatory networks in cancer as a non‑canonical aspect of miRNA action. Further research into this aspect may be critical for understanding the role of nuclear miRNAs in the development of human cancers.

Keywords: Argonaute 2; nuclear miRNAs; promoter; transcriptional regulation; tumorigenesis.