Abstract
Natural antisense transcripts (NATs), which are transcribed from opposite strands of DNA with partial or complete overlap, affect multiple stages of gene expression, from epigenetic to post-translational modifications. NATs are dysregulated in various types of cancer, and an increasing number of studies focusing on NATs as pivotal regulators of the hallmarks of cancer and as promising candidates for cancer therapy are just beginning to unravel the mystery. Here, we summarize the existing knowledge on NATs to highlight their underlying mechanisms of functions in cancer biology, discuss their potential roles in therapeutic application, and explore future research directions.
Highlights
Introduction to natural antisense transcripts (NATs) in cancerThe term cancer refers to a group of genetic diseases, in which cell signaling networks are modified, resulting in disorganized cell homeostasis and uncontrolled growth [22, 23]
NATs are dysregulated in various cancers and are implicated in multiple malignant phenotypes
Recent studies demonstrate that NATs are emerging as important players in the hallmarks of cancer via their involvement in diverse stages of gene expression regulation, from controlling epigenetic modifications to modulating mRNA post-translational modifications (PTMs)
Summary
Introduction to NATs in cancerThe term cancer refers to a group of genetic diseases, in which cell signaling networks are modified, resulting in disorganized cell homeostasis and uncontrolled growth [22, 23]. Accumulating evidence has demonstrated that NATs act as biomarkers for cellular pathophysiologies, provide diagnostic and prognostic value, and reveal promising therapeutic targets for cancer [11, 12]. Mounting evidence has demonstrated that non-coding RNAs (ncRNAs) can modulate the expression of proteincoding RNA and play indispensable roles in various biological processes, including tumorigenesis, metastasis, and therapeutic resistance [4–7]. 200 nucleotides is used as the biophysical threshold for separating long ncRNAs (lncRNAs) from short ncRNAs. The lncRNAs are further divided into different subclasses, and include intronic lncRNAs, bidirectional lncRNAs, intergenic lncRNAs, enhancer RNAs, circular RNAs (circRNAs), pseudogenes, sense lncRNAs, and natural antisense transcripts (NATs), based on their original genomic locations or their relationships with protein-coding genes. For more details on lncRNAs classification, please refer to [8, 9]
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