Pseudogene-derived lncRNAs: emerging regulators of gene expression

Milligan, Michael J.; Lipovich, Leonard

doi:10.3389/fgene.2014.00476

Cited by 108 publications

(94 citation statements)

References 70 publications

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“…Clearly, a non-coding transcript that shares a high degree of homology with a coding gene is likely to share many of its MREs and therefore pseudogenes are good candidates to act as ceRNAs. Indeed, this seems to be the case [13], [47], [48]. Examples of such lncRNAs include a pseudogene homologous to the gene encoding tumour suppressor phosphatase and tensin homologue ( PTEN ), which contains multiple MREs within the 3′UTR shared with the coding gene [48], as well as pseudogenes homologous to the 3′UTRs of the genes encoding tumour suppressor candidate 2 ( TUSC2 ) [49] and forkhead box protein O1 ( FOXO1 ) [50].…”

Section: Functions Of Lncrnamentioning

confidence: 99%

Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA

Dykes

Emanueli

2017

Genomics, Proteomics &Amp; Bioinformatics

723

511

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Advances in genomics technology over recent years have led to the surprising discovery that the genome is far more pervasively transcribed than was previously appreciated. Much of the newly-discovered transcriptome appears to represent long non-coding RNA (lncRNA), a heterogeneous group of largely uncharacterised transcripts. Understanding the biological function of these molecules represents a major challenge and in this review we discuss some of the progress made to date. One major theme of lncRNA biology seems to be the existence of a network of interactions with microRNA (miRNA) pathways. lncRNA has been shown to act as both a source and an inhibitory regulator of miRNA. At the transcriptional level, a model is emerging whereby lncRNA bridges DNA and protein by binding to chromatin and serving as a scaffold for modifying protein complexes. Such a mechanism can bridge promoters to enhancers or enhancer-like non-coding genes by regulating chromatin looping, as well as conferring specificity on histone modifying complexes by directing them to specific loci.

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Section: Functions Of Lncrnamentioning

confidence: 99%

Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA

Dykes

Emanueli

2017

Genomics, Proteomics &Amp; Bioinformatics

723

511

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“…LncRNAs may be transcribed as partial or whole natural antisense transcripts (NAT) of coding genes, or they might be located between genes or within introns. Some lncRNAs originate from so-called pseudogenes (Milligan and Lipovich, 2014). They can be described as intergenic, intronic, overlapping, antisense, bidirectional or processed (Mattick and Rinn, 2015; Peschansky and Wahlestedt, 2014).…”

Section: Current Challenges and Future Directionsmentioning

confidence: 99%

Gene transfer to the outflow tract

Dang

Loewen

Parikh

et al. 2017

Experimental Eye Research

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Elevated intraocular pressure is the primary cause of open angle glaucoma. Outflow resistance exists within the trabecular meshwork but also at the level of Schlemm's canal and further downstream within the outflow system. Viral vectors allow to take advantage of naturally evolved, highly efficient mechanisms of gene transfer, a process that is termed transduction. They can be produced at biosafety level 2 in the lab using protocols that have evolved considerably over the last 15 to 20 years. Applied by an intracameral bolus, vectors follow conventional as well as uveoscleral outflow pathways. They may affect other structures in the anterior chamber depending on their transduction kinetics which can vary among species when using the same vector. Not all vectors can express long-term, a desirable feature to address the chronicity of glaucoma. Vectors that integrate into the genome of the target cell can achieve transgene function for the life of the transduced cell but are mutagenic by definition. The most prominent long-term expressing vector systems are based on lentiviruses that are derived from HIV, FIV, or EIAV. Safety considerations make non-primate lentiviral vector systems easier to work with as they are not derived from human pathogens. Non-integrating vectors are subject to degradation and attritional dilution during cell division. Lentiviral vectors have to integrate in order to express while adeno-associated viral vectors (AAV) often persist as intracellular concatemers but may also integrate. Adeno- and herpes viral vectors do not integrate and earlier generation systems might be relatively immunogenic. Nonviral methods of gene transfer are termed transfection with few restrictions of transgene size and type but often a much less efficient gene transfer that is also short-lived. Traditional gene transfer delivers exons while some vectors (lentiviral, herpes and adenoviral) allow transfer of entire genes that include introns. Recent insights have highlighted the role of non-coding RNA, most prominently, siRNA, miRNA and lncRNA. SiRNA is highly specific, miRNA is less specific, while lncRNA uses highly complex mechanisms that involve secondary structures and intergenic, intronic, overlapping, antisense, and bidirectional location. Several promising preclinical studies have targeted the RhoA or the prostaglandin pathway or modified the extracellular matrix. TGF-β and glaucoma myocilin mutants have been transduced to elevate the intraocular pressure in glaucoma models. Cell based therapies have started to show first promise. Past approaches have focused on the trabecular meshwork and the inner wall of Schlemm's canal while new strategies are concerned with modification of outflow tract elements that are downstream of the trabecular meshwork.

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“…3 Moreover, the patients with CRC accompanied by distant metastasis were documented with a 5-year survival of less than 50%, which stated the significance of diagnosing early CRC. [5][6][7][8][9] Intriguingly, the lncRNAs were increasingly concerned regarding their modulation of tumorigenesis. 4 In accordance with the encyclopedia of DNA elements initiated in 2003, approximately 65% of genes were transcribed into noncoding RNAs (ncRNAs), and the ncRNAs that possessed more than 200 nucleotides were acknowledged as long noncoding RNAs (lncRNAs).…”

Section: Introductionmentioning

confidence: 99%

Regulatory effects of lncRNA ATB targeting miR‐200c on proliferation and apoptosis of colorectal cancer cells

Gao

Zhou

Wang

et al. 2019

J of Cellular Biochemistry

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This investigation was intended to elucidate whether long noncoding RNA (lncRNA)‐activated by transforming growth factor‐β (ATB) interacting with miR‐200c could mediate colorectal cancer (CRC) progression, offering potential strategies for diagnosing and treating CRC. Here totally 315 patients with CRC were recruited, and their CRC tissues and adjacent normal tissues were gathered. Concurrently, four colon cancer cell lines (ie, SW620, Lovo, HCT116, and SW480) and the human colon mucosal epithelial cell line (NCM460) were also purchased. Moreover, si‐ATB, si‐NC, miR‐200c mimic, miR‐200c inhibitor, and miR‐NC were prepared for transfection into the CRC cells, and their effects on CRC cell lines were evaluated based on the conduction of 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay, colony formation assay, and flow cytometry assay. Eventually, the Luciferase reporter gene assay was carried out to judge if there existed a targeted relationship between ATB and miR‐200c. The results of Cox regression analyses suggested that overexpressed lncRNA ATB, underexpressed miR‐200c, poor tumor differentiation, lymph‐vascular invasion, and perineural invasion were symbolic of shortened survival of the patients with CRC (all P < .05). Besides, transfection of pcDNA3.1‐ATB and miR‐200c inhibitor could boost the viability and proliferation of Lovo and SW620 cell lines (all P < .05). Meanwhile, the expressions of p53 and p21 were also reduced under treatments of pcDNA3.1‐ATB and miR‐200c inhibitor (P < .05). In addition, CDK2 seemed to reverse the contribution of miR‐200c to intensifying viability and proliferation of Lovo and SW420 cell lines (P < .05). Furthermore, ATB might downregulate miR‐200c expression by targeting it (P < .05), and CDK2 was subjected to dual regulation of both ATB and miR‐200c (P < .05). In conclusion, the lncRNA ATB/miR‐200c/CDK2 signaling was responsible for intensified proliferation and prohibited apoptosis of CRC cells, which might provide effective approaches for diagnosing and treating CRC.

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Pseudogene-derived lncRNAs: emerging regulators of gene expression

Cited by 108 publications

References 70 publications

Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA

Transcriptional and Post-Transcriptional Gene Regulation by Long Non-Coding RNA

Gene transfer to the outflow tract

Regulatory effects of lncRNA ATB targeting miR‐200c on proliferation and apoptosis of colorectal cancer cells

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