Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark
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(2020) 39:187
REVIEW
Open Access
Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark Shanshan Zhao1, Xue Zhang2, Shuo Chen3 and Song Zhang4,5*
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. Keywords: Natural antisense transcripts, NATs, Cancer, Hallmarks of cancer
Background High-throughput RNA sequencing has revealed the universal transcriptional information of the human genome, of which non-coding sequences account for 98% [1]. Non-coding sequences were previously considered as “junk DNA” due to their low expression levels, unknown functions, and heterogeneity [2, 3]. However, 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]. ncRNAs are classified into two groups based on the transcript length. In general, 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 * Correspondence: [email protected] 4 Department of Thoracic Surgery, The First Affiliated Hospital of China Medical University, 110001 Shenyang, Liaoning, China 5 Department of Environmental and Occupational Health, School of Public Health, China Medical University, 110122 Shenyang, Liaoning, China Full list of author information is available at the end of the article
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]. NATs are RNA molecules transcribed from the opposite strands of DNA that partially or completely overlap with the sense RNA [10, 11]. Investigations of NATs have been initiated in recent years due to the development of high-throughput sequencing, and NATs have attracted increasing interest due to their significant roles in diverse pathophysiological processes [11]. Many NATs were first annotated as lncRNAs, and therefore described as a subclass of lncRNA [12, 13]. Even so, NATs can also be short ncRNAs [11, 14] or proteincoding genes [15]. The incomplete overla
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