Non-coding antisense transcripts: fine regulation of gene expression in cancer

Santos, Filipe Neves dos; Capela, Ana Maria; Mateus, Francisca; Nóbrega-Pereira, Sandrina; Jesus, Bruno Bernardes de

doi:10.1016/j.csbj.2022.10.009

Cited by 10 publications

(7 citation statements)

References 137 publications

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“…Natural antisense transcripts (NATs) are coding or non-coding RNA sequences transcribed from the opposite direction from the same genomic locus as overlapped genes and seem to play important roles in pathological processes ( Latgé et al, 2018 ; Santos et al, 2022 ) through various molecular mechanisms ( Zhao et al, 2020 ; Krappinger et al, 2021 ; Molias et al, 2021 ). Only in recent years due to evolvement of high-throughput strand-specific sequencing technologies lowly expressed NATs (to which antisense long non-coding RNAs belong) attracted attention as candidate biomarkers and therapeutic targets in cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Natural antisense transcripts (NATs) are coding or non-coding RNA (ncRNA) sequences that are transcribed from the opposite strand of non-protein coding (nc) or protein coding (pc) genes and are complementary to or overlap with either protein-coding or non-coding transcript ( Latgé et al, 2018 ; Santos et al, 2022 ). NATs can modulate the expression of their sense gene pairs (sense/antisense pairing) or of several related genes and are implicated in a broad variety of biological and pathological processes, including oncogenic progression ( Guttman et al, 2009 ; Sun et al, 2017 ; Zhao et al, 2020 ; Krappinger et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Antisense lncRNA CHROMR is linked to glioma patient survival

Širvinskas

Steponaitis²,

Stakaitis³

et al. 2023

Front. Mol. Biosci.

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Background: Natural non-coding antisense transcripts (ncNATs) are long non-coding RNAs (lncRNA) transcribed from the opposite strand of a separate protein coding or non-coding gene. As such, ncNATs can increase overlapping mRNA (and the coded protein) levels by stabilizing mRNA, absorbing inhibitory miRNAs and protecting the mRNA from degradation, or conversely decrease mRNA (or protein) levels by directing the mRNA towards degradation or inhibiting protein translation. Recently, growing numbers of ncNATs were shown to be dysregulated in cancerous cells, however, actual impact of ncNATs on cancer progression remains largely unknown. We therefore investigated gene expression levels of natural antisense lncRNA CHROMR (Cholesterol Induced Regulator of Metabolism RNA) and its sense protein coding gene PRKRA (Protein Activator of Interferon Induced Protein Kinase EIF2AK2) in gliomas. Next, we checked CHROMR effect on the survival of glioma patients.Methods: We performed RNA-seq on post-surgical tumor samples from 26 glioma patients, and normal brain tissue. Gene expression in TPM values were extracted for CHROMR and PRKRA genes. These data were validated using the TCGA and GTEx gene expression databases.Results: The gene expression level of ncNAT lncRNA CHROMR in glioma tissue was significantly higher compared to healthy brain tissue, while the expression of its sense counterpart protein coding PRKRA mRNA did not differ between glioma and healthy samples. Survival analysis showed lower survival rates in patients with low mRNA PRKRA/lncRNA CHROMR gene expression ratio compared to high ratio showing a link between lncRNA CHROMR and glioma patient survival prognosis.Conclusion: Here we show that elevated levels of lncRNA CHROMR (i.e., low ratio of mRNA PRKRA/lncRNA CHROMR) is associated with poor prognosis for glioma patients.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antisense lncRNA CHROMR is linked to glioma patient survival

Širvinskas

Steponaitis²,

Stakaitis³

et al. 2023

Front. Mol. Biosci.

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“…The antisense strand of an RNA molecule is a sequence of nucleotides complementary to a gene’s sense strand. Antisense RNA may affect splicing because of RNA-RNA interactions, in which it may build double-stranded RNA structures with the sense RNA ( Santos et al, 2022 ). By forming complementary base pairs with pre-mRNA, antisense RNA molecules may interfere with correctly identifying splice sites and splicing regulatory elements.…”

Section: Function Of Antisense Rnamentioning

confidence: 99%

“…By forming complementary base pairs with pre-mRNA, antisense RNA molecules may interfere with correctly identifying splice sites and splicing regulatory elements. Exon inclusion or exclusion is regulated by the degree to which this interaction promotes or inhibits the use of certain splice sites ( Santos et al, 2022 ). Traditionally, NATs interact with certain splicing factors to regulate alternative splicing ( Romero-Barrios et al, 2018 ).…”

Section: Function Of Antisense Rnamentioning

confidence: 99%

Recent insights into the functions and mechanisms of antisense RNA: emerging applications in cancer therapy and precision medicine

Rehman,

Ullah,

Zhang

et al. 2024

Front. Chem.

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The antisense RNA molecule is a unique DNA transcript consisting of 19–23 nucleotides, characterized by its complementary nature to mRNA. These antisense RNAs play a crucial role in regulating gene expression at various stages, including replication, transcription, and translation. Additionally, artificial antisense RNAs have demonstrated their ability to effectively modulate gene expression in host cells. Consequently, there has been a substantial increase in research dedicated to investigating the roles of antisense RNAs. These molecules have been found to be influential in various cellular processes, such as X-chromosome inactivation and imprinted silencing in healthy cells. However, it is important to recognize that in cancer cells; aberrantly expressed antisense RNAs can trigger the epigenetic silencing of tumor suppressor genes. Moreover, the presence of deletion-induced aberrant antisense RNAs can lead to the development of diseases through epigenetic silencing. One area of drug development worth mentioning is antisense oligonucleotides (ASOs), and a prime example of an oncogenic trans-acting long noncoding RNA (lncRNA) is HOTAIR (HOX transcript antisense RNA). NATs (noncoding antisense transcripts) are dysregulated in many cancers, and researchers are just beginning to unravel their roles as crucial regulators of cancer’s hallmarks, as well as their potential for cancer therapy. In this review, we summarize the emerging roles and mechanisms of antisense RNA and explore their application in cancer therapy.

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“…discovered that the reduced production of NATs led to a decrease in the expression of genes that promote cancer [ 7 ]. A further investigation carried out by Santos et al revealed that NATs have demonstrated a reduction in cancer occurrence when expressed at low levels [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention

Ali,

Khatoon,

Shao

et al. 2023

RNA Biology

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Antisense transcription, a prevalent occurrence in mammalian genomes, gives rise to natural antisense transcripts (NATs) as RNA molecules. These NATs serve as agents of diverse transcriptional and post-transcriptional regulatory mechanisms, playing crucial roles in various biological processes vital for cell function and immune response. However, when their normal functions are disrupted, they can contribute to human diseases. This comprehensive review aims to establish the molecular foundation linking NATs to the development of disorders like cancer, neurodegenerative conditions, and cardiovascular ailments. Additionally, we evaluate the potential of oligonucleotide-based therapies targeting NATs, presenting both their advantages and limitations, while also highlighting the latest advancements in this promising realm of clinical investigation. Abbreviations: NATs- Natural antisense transcripts, PRC1- Polycomb Repressive Complex 1, PRC2- Polycomb Repressive Complex 2, ADARs- Adenosine deaminases acting on RNA, BDNF-AS- Brain-derived neurotrophic factor antisense transcript, ASOs- Antisense oligonucleotides, SINEUPs- Inverted SINEB2 sequence-mediated upregulating molecules, PTBP1- Polypyrimidine tract binding protein-1, HNRNPK- heterogeneous nuclear ribonucleoprotein K, MAPT-AS1- microtubule-associated protein tau antisense 1, KCNQ1OT- (KCNQ1 opposite strand/antisense transcript 1, ERK- extracellular signal-regulated kinase 1, USP14- ubiquitin-specific protease 14, EGF- Epidermal growth factor, LSD1- Lysine Specific Demethylase 1, ANRIL- Antisense Noncoding RNA in the INK4 Locus, BWS- Beckwith-Wiedemann syndrome, VEGFA- Vascular Endothelial Growth component A

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Non-coding antisense transcripts: fine regulation of gene expression in cancer

Cited by 10 publications

References 137 publications

Antisense lncRNA CHROMR is linked to glioma patient survival

Antisense lncRNA CHROMR is linked to glioma patient survival

Recent insights into the functions and mechanisms of antisense RNA: emerging applications in cancer therapy and precision medicine

Therapeutic potential of natural antisense transcripts and various mechanisms involved for clinical applications and disease prevention

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