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Cells
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Gene Fusions and Chimeric RNA in Cancers and Complex Diseases
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Gene Fusions and Chimeric RNA in Cancers and Complex Diseases

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: closed (15 February 2022) | Viewed by 7282

Special Issue Editor

Dr. Milana Frenkel-Morgenstern

E-Mail Website
Guest Editor
Azrieli Faculty of Medicine, Bar-Ilan University, Safad, Israel
Interests: experimental systems biology; genome and cancer biology; bioinformatics of complex diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The special issue provides the most updated methods and observations in gene fusions and chimeric RNAs for their functional characterization and role in different cancer types. The issue will describe chimeric RNAs as transcripts combining two distinct parental genes and characterized by the unique junction sites. The unique observations for chimeric RNAs and fusions will be explored at all the levels as chromosomal translocations, trans-splicing, and production of fusion proteins. We will emphasize the unique techniques for the identification and characterization through bioinformatics tools, as well as the experimental validation using RT-PCR, mass spectrometry techniques for the fusion protein validation, and more.

We will incorporate articles on the functional as well as mechanistic studies of chimeric RNAs and translational applications in modern Genomics and Personalized Therapy techniques. The issue will provide most advance topics in fusions, chimeric RNAs and their protein products. The issue will guide the field of Cancer Research as well as complex diseases. It will be an inspiration to researchers seeking to extensive knowledge of the remarkable features of chimeric RNA world.

Dr. Milana Frenkel-Morgenstern
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • gene-gene fusions
  • chimeric RNA
  • cancer
  • complex diseases

Published Papers (3 papers)

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Research

11 pages, 3045 KiB  
Article
The Landscape of Novel Expressed Chimeric RNAs in Rheumatoid Arthritis
by Rajesh Detroja, Sumit Mukherjee and Milana Frenkel-Morgenstern
Cells 2022, 11(7), 1092; https://doi.org/10.3390/cells11071092 - 24 Mar 2022
Cited by 4 | Viewed by 2114
Abstract
In cancers and other complex diseases, the fusion of two genes can lead to the production of chimeric RNAs, which are associated with disease development. Several recurrent chimeric RNAs are expressed in different cancers and are thus used for clinical cancer diagnosis. Rheumatoid [...] Read more.
In cancers and other complex diseases, the fusion of two genes can lead to the production of chimeric RNAs, which are associated with disease development. Several recurrent chimeric RNAs are expressed in different cancers and are thus used for clinical cancer diagnosis. Rheumatoid arthritis (RA) is an immune-mediated joint disorder resulting in synovial inflammation and joint destruction. Despite advances in therapy, many patients do not respond to treatment and present persistent inflammation. Understanding the landscape of chimeric RNA expression in RA patients could provide a better insight into RA pathogenesis, which might provide better treatment strategies and tailored therapies. Accordingly, we analyzed the publicly available RNA-seq data of synovium tissue from 151 RA patients and 28 healthy controls and were able to identify 37 recurrent chimeric RNAs found to be expressed in at least 3 RA samples. Furthermore, the parental genes of these 37 recurrent chimeric RNAs were found to be differentially expressed and enriched in immune-related processes, such as adaptive immune response and the positive regulation of B-cell activation. Interestingly, the appearance of 5 coding and 23 non-coding chimeric RNAs might be associated with regulating their parental gene expression, leading to the generation of dysfunctional immune responses, such as inflammation and bone destruction. Therefore, in this paper, we present the first study to demonstrate the novel chimeric RNAs that are highly expressed and functional in RA. Full article
(This article belongs to the Special Issue Gene Fusions and Chimeric RNA in Cancers and Complex Diseases)
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11 pages, 1496 KiB  
Article
Chimeric RNA Design Principles for RNA-Mediated Gene Fusion
by Sachin Kumar Gupta and Laising Yen
Cells 2022, 11(6), 1002; https://doi.org/10.3390/cells11061002 - 16 Mar 2022
Viewed by 1911
Abstract
One common genetic alteration in cancer is gene fusion resulting from chromosomal translocations. The mechanisms that create such oncogenic fusion genes are not well understood. Previously, we provided the direct evidence that expression of a designed chimeric RNA can drive the formation of [...] Read more.
One common genetic alteration in cancer is gene fusion resulting from chromosomal translocations. The mechanisms that create such oncogenic fusion genes are not well understood. Previously, we provided the direct evidence that expression of a designed chimeric RNA can drive the formation of TMPRSS2-ERG gene fusion. Central to this RNA-mediated gene fusion mechanism is a proposed three-way junction formed by RNA/DNA hybrid and the intergenic DNA stem formed by target genes. In this study, we determined the important parameters for chimeric RNA-mediated gene fusion using TMPRSS2-ERG fusion gene as the model. Our results indicate that both the chimeric RNA lengths and the sizes of unpaired bulges play important roles in inducing TMPRSS2-ERG gene fusion. The optimal length of unpaired bulges was about 35 nt, while the optimal chimeric RNA length was about 50 nt for targeting. These observations were consistent regardless of the target locations within TMPRSS2 and ERG genes. These empirically determined parameters provide important insight for searching cellular RNAs that may initiate oncogenic fusion genes. The knowledge could also facilitate the development of useful genomic technology for manipulating mammalian genomes. Full article
(This article belongs to the Special Issue Gene Fusions and Chimeric RNA in Cancers and Complex Diseases)
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10 pages, 1719 KiB  
Article
Generation and Application of Inducible Chimeric RNA ASTN2-PAPPAas Knockin Mouse Model
by Yichen Luo, Liang Du, Zhimeng Yao, Fan Liu, Kai Li, Feifei Li, Jianlin Zhu, Robert P. Coppes, Dianzheng Zhang, Yunlong Pan, Shegan Gao and Hao Zhang
Cells 2022, 11(2), 277; https://doi.org/10.3390/cells11020277 - 14 Jan 2022
Cited by 2 | Viewed by 2503
Abstract
Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of [...] Read more.
Chimeric RNAs (chiRNAs) play many previously unrecognized roles in different diseases including cancer. They can not only be used as biomarkers for diagnosis and prognosis of various diseases but also serve as potential therapeutic targets. In order to better understand the roles of chiRNAs in pathogenesis, we inserted human sequences into mouse genome and established a knockin mouse model of the tamoxifen-inducible expression of ASTN2-PAPPA antisense chimeric RNA (A-PaschiRNA). Mice carrying the A-PaschiRNA knockin gene do not display any apparent abnormalities in growth, fertility, histological, hematopoietic, and biochemical indices. Using this model, we dissected the role of A-PaschiRNA in chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced carcinogenesis of esophageal squamous cell carcinoma (ESCC). To our knowledge, we are the first to generate a chiRNA knockin mouse model using the Cre-loxP system. The model could be used to explore the roles of chiRNA in pathogenesis and potential targeted therapies. Full article
(This article belongs to the Special Issue Gene Fusions and Chimeric RNA in Cancers and Complex Diseases)
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