Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark

Zhao, Shanshan; Zhang, Xue; Chen, Shuo; Zhang, Song

doi:10.1186/s13046-020-01700-0

Cited by 44 publications

(46 citation statements)

References 186 publications

(173 reference statements)

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“…In the ChiTaRS database, MYC was found to generate one SAS chimera, while EGFR can generate two, and TP53 can generate three such chimera. Several natural antisense transcripts (NATs) were identified for MYC ( 88 , 89 ), EGFR ( 90 , 91 ) and TP53 ( 92 , 93 ), which are involved in the antisense‐mediated regulation of these genes and play pivotal roles in cancer ( 94 ). Therefore, it is possible that trans-splicing could promote the fusion of the sense and antisense transcripts of the same gene and produce sense-antisense transcripts.…”

Section: Resultsmentioning

confidence: 99%

Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells

Mukherjee

Detroja

Balamurali

et al. 2021

NAR Genomics and Bioinformatics

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Many human genes are transcribed from both strands and produce sense-antisense gene pairs. Sense-antisense (SAS) chimeric transcripts are produced upon the coalescing of exons/introns from both sense and antisense transcripts of the same gene. SAS chimera was first reported in prostate cancer cells. Subsequently, numerous SAS chimeras have been reported in the ChiTaRS-2.1 database. However, the landscape of their expression in human cells and functional aspects are still unknown. We found that longer palindromic sequences are a unique feature of SAS chimeras. Structural analysis indicates that a long hairpin-like structure formed by many consecutive Watson-Crick base pairs appears because of these long palindromic sequences, which possibly play a similar role as double-stranded RNA (dsRNA), interfering with gene expression. RNA–RNA interaction analysis suggested that SAS chimeras could significantly interact with their parental mRNAs, indicating their potential regulatory features. Here, 267 SAS chimeras were mapped in RNA-seq data from 16 healthy human tissues, revealing their expression in normal cells. Evolutionary analysis suggested the positive selection favoring sense-antisense fusions that significantly impacted the evolution of their function and structure. Overall, our study provides detailed insight into the expression landscape of SAS chimeras in human cells and identifies potential regulatory features.

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Section: Resultsmentioning

confidence: 99%

Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells

Mukherjee

Detroja

Balamurali

et al. 2021

NAR Genomics and Bioinformatics

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“…Previous evidence has shown that many protein-coding mRNAs have natural antisense transcripts and that these non-coding RNAs account for most of the length of each mRNA. 21,22 Natural antisense transcript RNAs (NATs) are closely associated with the occurrence and development of cancer. For instance, NKX2-1-AS1 upregulates oncogene NKX2-1 and promotes the proliferation of lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

LncRNA FAM83A‐AS1 promotes lung adenocarcinoma progression by enhancing the pre‐mRNA stability of FAM83A

Wang

Zhao

et al. 2021

Thoracic Cancer

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Background Lung cancer is the leading cause of cancer deaths worldwide. Long non‐coding RNAs (lncRNAs) affect a series of cellular biological processes, including oncogene function promotion. In this study, we explored the functions and mechanisms of FAM83A antisense RNA 1 (FAM83A‐AS1) in non‐small cell lung cancer (NSCLC) progression. Methods The expression of FAM83A‐AS1and FAM83A mRNA was analyzed using the Cancer Genome Atlas (TCGA) data. Proliferation, migration, invasion and Western blotting were measured after treatment with overexpressed or knockdown FAM83A‐AS1. To determine the relationship between FAM83A‐AS1 and FAM83A, RNase protection assay (RPA), amanitin treatment, RNA pulldown assay and RNA immunoprecipitation (RIP) assay were performed. Results High expression of FAM83A‐AS1 in lung adenocarcinoma (LUAD) was closely associated with low overall survival (OS) and progression‐free survival (PFS). Functionally, high FAM83A‐AS1 expression increased LUAD cell proliferation and metastasis, indicating that FAM83A‐AS1 exerted its oncogenic functions. Furthermore, FAM83A‐AS1 promoted NSCLC progression via ERK signaling pathways. Mechanistically, FAM83A‐AS1 post‐transcriptionally increased FAM83A expression by enhancing pre‐mRNA stability. FAM83A‐AS1 enhanced FAM83A mRNA stability not only by forming an RNA duplex but also by binding to FBL. Conclusions We determined that FAM83A‐AS1 increased FAM83A expression by enhancing FAM83A pre‐mRNA stability and promoted the tumorigenesis of LUAD.

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“…This alternate isoform retains the IRES and has increased translational efficiency when compared to the spliced isoform without the IRES. Alterations in regulatory mechanisms resulting in the overexpression of ZEB2-AS have been associated with acute myeloid leukemia [97], bladder cancer [98] and other cancers [99].…”

Section: Examples Of Nats In Eukaryotic Cell Systemsmentioning

confidence: 99%

HIV-1 Natural Antisense Transcription and Its Role in Viral Persistence

Sklutuis

Groebner

et al. 2021

Viruses

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Natural antisense transcripts (NATs) represent a class of RNA molecules that are transcribed from the opposite strand of a protein-coding gene, and that have the ability to regulate the expression of their cognate protein-coding gene via multiple mechanisms. NATs have been described in many prokaryotic and eukaryotic systems, as well as in the viruses that infect them. The human immunodeficiency virus (HIV-1) is no exception, and produces one or more NAT from a promoter within the 3’ long terminal repeat. HIV-1 antisense transcripts have been the focus of several studies spanning over 30 years. However, a complete appreciation of the role that these transcripts play in the virus lifecycle is still lacking. In this review, we cover the current knowledge about HIV-1 NATs, discuss some of the questions that are still open and identify possible areas of future research.

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Natural antisense transcripts in the biological hallmarks of cancer: powerful regulators hidden in the dark

Cited by 44 publications

References 186 publications

Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells

Computational analysis of sense-antisense chimeric transcripts reveals their potential regulatory features and the landscape of expression in human cells

LncRNA FAM83A‐AS1 promotes lung adenocarcinoma progression by enhancing the pre‐mRNA stability of FAM83A

HIV-1 Natural Antisense Transcription and Its Role in Viral Persistence

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