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State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in...
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State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Tumor Microenvironment".

Deadline for manuscript submissions: 10 February 2025 | Viewed by 5188

Special Issue Editors

Dr. Antonis Giakountis

E-Mail Website
Guest Editor
Laboratory of Molecular Biology and Genomics, Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece
Interests: lncRNA-mediated transcriptional regulation; RNA–chromatin interactions; chromatin architecture; transcriptional and epigenetic regulation in cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Nikolaos Balatsos

E-Mail Website
Guest Editor
Department of Biochemistry and Biotechnology, University of Thessaly, Biopolis - Mezourlo, 41500 Larisa, Greece
Interests: regulation of mRNA stability and degradation; lung cancer

Special Issue Information

Dear Colleagues,

One fundamental conceptualization in the post-genomic era is the observation that 90% of the human genome is transcriptionally active, yet less than 2% of its sequence encodes for proteins. Extensive research has revealed numerous examples of functional non-coding transcripts, broadly categorized as short or long non-coding RNAs based on transcript length, highlighting the complexity of RNA-mediated regulation in maintaining physiological homeostasis or inducing its pathological manifestation.

Since their discovery, non-coding RNAs have been associated with cancer initiation, progression or inhibition. Their functional complexity, combined with their cancer-specific regulation and detection in the body fluids of patients, highlight them as sensitive and non-invasive diagnostic, prognostic and therapeutic biomarkers.

This Special Issue will emphasize the role of non-coding RNAs along with their associated predisposing regulatory mutations, focusing on novel strategies designed to unveil their molecular function and utilization as non-invasive biomarkers for ribodiagnostic, prognostic and therapeutic application against human tumors.

Dr. Antonis Giakountis
Dr. Nikolaos Balatsos
Guest Editors

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 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. Cancers 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 2900 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

  • long non-coding RNAs
  • miRNAs
  • regulatory non-coding variants
  • ribodiagnostics
  • RNA therapeutics
  • targeted therapy
  • cancer

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Published Papers (3 papers)

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Research

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22 pages, 5008 KiB  
Article
Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma
by Yoko Hagihara, Yuya Tomioka, Takayuki Suetsugu, Masahiro Shinmura, Shunsuke Misono, Yusuke Goto, Naoko Kikkawa, Mayuko Kato, Hiromasa Inoue, Keiko Mizuno and Naohiko Seki
Cancers 2023, 15(23), 5571; https://doi.org/10.3390/cancers15235571 - 24 Nov 2023
Cited by 2 | Viewed by 1531
Abstract
Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. [...] Read more.
Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD. Full article
(This article belongs to the Special Issue State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in Cancer)
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15 pages, 6848 KiB  
Article
Functional In Vivo Screening Identifies microRNAs Regulating Metastatic Dissemination of Prostate Cancer Cells to Bone Marrow
by Tina Catela Ivkovic, Helena Cornella, Gjendine Voss, Anson Ku, Margareta Persson, Robert Rigo, Sofia K. Gruvberger-Saal, Lao H. Saal and Yvonne Ceder
Cancers 2023, 15(15), 3892; https://doi.org/10.3390/cancers15153892 - 31 Jul 2023
Cited by 1 | Viewed by 1321
Abstract
Distant metastasis is the major cause of cancer-related deaths in men with prostate cancer (PCa). An in vivo functional screen was used to identify microRNAs (miRNAs) regulating metastatic dissemination of PCa cells. PC3 cells transduced with pooled miRZiP™ lentivirus library (anti-miRNAs) were injected [...] Read more.
Distant metastasis is the major cause of cancer-related deaths in men with prostate cancer (PCa). An in vivo functional screen was used to identify microRNAs (miRNAs) regulating metastatic dissemination of PCa cells. PC3 cells transduced with pooled miRZiP™ lentivirus library (anti-miRNAs) were injected intraprostatic to 13 NSG mice followed by targeted barcode/anti-miR sequencing. PCa cells in the primary tumours showed a homogenous pattern of anti-miRNAs, but different anti-miRNAs were enriched in liver, lung, and bone marrow, with anti-miR-379 highly enriched in the latter. The bone metastasis-promoting phenotype induced by decreased miR-379 levels was also confirmed in a less metastatic PCa cell line, 22Rv1, where all mice injected intracardially with anti-miR-379-22Rv1 cells developed bone metastases. The levels of miR-379 were found to be lower in bone metastases compared to primary tumours and non-cancerous prostatic tissue in a patient cohort. In vitro functional studies suggested that the mechanism of action was that reduced levels of miR-379 gave an increased colony formation capacity in conditions mimicking the bone microenvironment. In conclusion, our data suggest that specific miRNAs affect the establishment of primary tumours and metastatic dissemination, with a loss of miR-379 promoting metastases in bone. Full article
(This article belongs to the Special Issue State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in Cancer)
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Review

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28 pages, 4230 KiB  
Review
RNA-Independent Regulatory Functions of lncRNA in Complex Disease
by Michaela Kafida, Maria Karela and Antonis Giakountis
Cancers 2024, 16(15), 2728; https://doi.org/10.3390/cancers16152728 - 31 Jul 2024
Viewed by 1546
Abstract
During the metagenomics era, high-throughput sequencing efforts both in mice and humans indicate that non-coding RNAs (ncRNAs) constitute a significant fraction of the transcribed genome. During the past decades, the regulatory role of these non-coding transcripts along with their interactions with other molecules [...] Read more.
During the metagenomics era, high-throughput sequencing efforts both in mice and humans indicate that non-coding RNAs (ncRNAs) constitute a significant fraction of the transcribed genome. During the past decades, the regulatory role of these non-coding transcripts along with their interactions with other molecules have been extensively characterized. However, the study of long non-coding RNAs (lncRNAs), an ncRNA regulatory class with transcript lengths that exceed 200 nucleotides, revealed that certain non-coding transcripts are transcriptional “by-products”, while their loci exert their downstream regulatory functions through RNA-independent mechanisms. Such mechanisms include, but are not limited to, chromatin interactions and complex promoter-enhancer competition schemes that involve the underlying ncRNA locus with or without its nascent transcription, mediating significant or even exclusive roles in the regulation of downstream target genes in mammals. Interestingly, such RNA-independent mechanisms often drive pathological manifestations, including oncogenesis. In this review, we summarize selective examples of lncRNAs that regulate target genes independently of their produced transcripts. Full article
(This article belongs to the Special Issue State-of-the-Art Strategies for Non-Coding RNA Function Detection and Regulation in Cancer)
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