International Journal of Molecular Sciences

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Dr. Simone Anfossi

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Guest Editor

Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Interests: molecular and cell immunology; non-coding RNA; extracellular vesicles; tumor microenvironment
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Dr. Linda Fabris

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Guest Editor

Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Interests: ncRNAs; ultra-conserved DNA regions

Special Issue Information

Dear Colleagues,

Cancer is a complex genetic disorder where the alteration of the expression of the genes drives functional changes in the biology of cells, leading to the development of cancer. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a relevant role in the regulation of gene expression. The aberrant expression of ncRNAs is frequently found in cancer cells, contributing to cancer development and progression. Aside from their localization inside cells, ncRNAs can also be found in the extracellular space as an intercellular messenger. Indeed, ncRNAs can be shuttled among the cells within the tumor microenvironment and even distant organs in a cell-free fashion, either encapsulated in extracellular vesicles (EVs) or complexed with lipoprotein. The delivery of ncRNAs can regulate recipient cells' gene expression and biological functions. The bidirectional communication between cancer cells and normal surrounding cells (immune, endothelial, epithelial, and stromal cells) is essential in regulating cancer progression. The study of the functional role of cellular and extracellular ncRNAs will help gain further insights into understanding the molecular mechanisms regulating cancer initiation and progression, as well as identifying new potential targets for novel cancer therapy.

Dr. Simone Anfossi
Dr. Linda Fabris
Guest Editors

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Keywords

ncRNAs
gene expression regulation
biological functions
extracellular vesicles
intercellular communication
cancer progression
tumor microenvironment

Published Papers (2 papers)

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Research

19 pages, 6122 KiB

Open AccessArticle

Locked Nucleic Acid Oligonucleotides Facilitate RNA•LNA-RNA Triple-Helix Formation and Reduce MALAT1 Levels

by Krishna M. Shivakumar, Gowthami Mahendran and Jessica A. Brown

Int. J. Mol. Sci. 2024, 25(3), 1630; https://doi.org/10.3390/ijms25031630 - 28 Jan 2024

Viewed by 1174

Abstract

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and multiple endocrine neoplasia-β (MENβ) are two long noncoding RNAs upregulated in multiple cancers, marking these RNAs as therapeutic targets. While traditional small-molecule and antisense-based approaches are effective, we report a locked nucleic acid (LNA)-based approach that targets the MALAT1 and MENβ triple helices, structures comprised of a U-rich internal stem-loop and an A-rich tract. Two LNA oligonucleotides resembling the A-rich tract (i.e., A₉GCA₄) were examined: an LNA (L15) and a phosphorothioate LNA (PS-L15). L15 binds tighter than PS-L15 to the MALAT1 and MENβ stem loops, although both L15 and PS-L15 enable RNA•LNA-RNA triple-helix formation. Based on UV thermal denaturation assays, both LNAs selectively stabilize the Hoogsteen interface by 5–13 °C more than the Watson–Crick interface. Furthermore, we show that L15 and PS-L15 displace the A-rich tract from the MALAT1 and MENβ stem loop and methyltransferase-like protein 16 (METTL16) from the METTL16-MALAT1 triple-helix complex. Human colorectal carcinoma (HCT116) cells transfected with LNAs have 2-fold less MALAT1 and MENβ. This LNA-based approach represents a potential therapeutic strategy for the dual targeting of MALAT1 and MENβ. Full article

(This article belongs to the Special Issue Functional Role of Non-coding RNAs in Cancer: Inside and outside Cells)

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16 pages, 9427 KiB

Open AccessArticle

Post-Radiotherapy Exosomal Non-Coding RNA and Hemograms for Early Death Prediction in Patients with Cervical Cancer

by Oyeon Cho

Int. J. Mol. Sci. 2024, 25(1), 126; https://doi.org/10.3390/ijms25010126 (registering DOI) - 21 Dec 2023

Viewed by 655

Abstract

Concurrent chemo-radiotherapy (CCRT) is linked with accelerated disease progression and early death (ED) in various cancers. This study aimed to assess the association of plasma levels of exosomal non-coding ribonucleic acid (RNA) (ncRNA) and blood cell dynamics with ED prediction in patients with cervical cancer undergoing CCRT. Using propensity score matching, a comparison of complete blood counts (CBCs) was performed among 370 CCRT-treated patients. Differences in ncRNA and messenger RNA (mRNA) expression before and after CCRT in 84 samples from 42 patients (cohort 2) were represented as logarithmic fold change (log₂FC). Networks were constructed to link the CBCs to the RNAs whose expression correlated with ED. From the key RNAs selected using multiple regression of all RNA combinations in the network, CBC dynamics-associated ncRNAs were functionally characterized using an enrichment analysis. Cohort 1 (120 patients) exhibited a correlation between elevated absolute neutrophil counts (ANC) and ED. Cohort 2 exhibited a prevalence of microRNA (miR)-574-3p and long intergenic non-protein coding (LINC)01003 ncRNA, whose expression correlated with ANC and hemoglobin values, respectively. Conversely, acyl-coenzyme A thioesterase 9 (ACOT9) mRNA was relevant to all CBC components. An integrative analysis of post-CCRT ncRNA levels and CBC values revealed that the patients with miR-574-3p-LINC01003-ACOT9 log₂FC) < 0 had a better prospect of 30-month disease-specific survival. These findings indicate that miR-574-3p and LINC01003 could serve as ED prognostic biomarkers. Full article

(This article belongs to the Special Issue Functional Role of Non-coding RNAs in Cancer: Inside and outside Cells)

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