MicroRNAs, tRNA Fragments, Long Non-coding and Circular RNAs: Pivotal Regulators of Gene Expression and Their Roles in Human Physiology and Disease

A topical collection in Biomedicines (ISSN 2227-9059). This collection belongs to the section "Cell Biology and Pathology".

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Dear Colleagues,

MicroRNAs (miRNAs) are single-stranded, small non-coding RNA molecules that epigenetically regulate gene expression, mostly through binding to the 3′ untranslated region (3′ UTR) of targeted messenger RNA (mRNA) molecules and, hence, mediating translational repression, usually combined with or followed by mRNA degradation. The human genome can produce more than a thousand of different miRNAs, which regulate approximately 70% of protein-coding genes, thereby controlling the activity and function of key signaling pathways and cellular processes such as cell proliferation, apoptosis, cell differentiation, and response to hypoxia. In fact, miRNAs can function either as oncogenes or tumor suppressors. From a clinical perspective, particular miRNAs can also serve as molecular biomarkers and therapeutic targets for several human diseases.

tRNA-derived RNA fragments are small non-coding RNAs specifically cleaved from transfer RNA (tRNAs), with a length of 14–48 nucleotides. They are classified into three main classes, namely the tRNA fragments (tRFs), the stress induced tRNA derived RNA fragments (tiRNAs), and the toxic small tRNA derived RNA fragments (tsRNAs). The tRNA molecules present a high differentiation in their cleavage sites, thus leading to several tRNA-derived RNA fragments varying in length and having distinct functions. They participate in translation regulation and gene silencing with a subsequent effect on cell viability and proliferation. Furthermore, they play a pivotal role in stress-induced situations.

Circular RNAs (circRNAs) are a neglected RNA type deriving from back-splicing. Initially, they were characterized as by-products of alternative splicing. However, the high-throughput analysis revolution uncovered their widespread expression, arousing the scientific interest. circRNAs have been designated as crucial modulators in several aspects of cell life, both in physiological and pathological states. CircRNAs are heavily involved in biological processes by acting either as sponges of miRNAs and RNA-binding proteins (RBPs) or by encoding for peptides. Especially, their miRNA-sponging activity implies that circRNAs can affect post-transcriptional gene regulation mediated by miRNAs. As studies regarding the intricate functions of circRNAs emerged, their association with multiple regulatory networks became evident, proving that these molecules play key roles in human disease development and may have wide clinical application.

Long noncoding RNAs (lncRNAs) are abundantly transcribed by the human genome. During the last decade, it has become evident that mutations and dysregulation of expression of lncRNAs significantly contribute to many human diseases. Alterations in the primary structure, secondary structure, and expression levels of lncRNAs as well as their cognate RNA-binding proteins have been shown to underlie the pathobiology of cancer, neurodegenerative, and cardiovascular diseases. Thus, recent scientific progress suggests that the involvement of lncRNAs in human diseases could be far more prevalent than previously thought.

This topic collection focuses on the information of the readers regarding the potential of miRNAs, tRNA-derived RNA fragments, circRNAs and other long non-coding RNAs to regulate protein-coding gene expression at a post-transcriptional level, in human physiological and pathological states. The authors are encouraged to submit their original research studies concerning this topic. Review articles will also be taken into consideration. We hope that this topic collection regarding the identity, biological role, and/or clinical utility of miRNAs, tRNA fragments, lncRNAs and circRNAs will arise the interest of the readers of this journal.

Dr. Christos K. Kontos
Guest Editor

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Keywords

  • circular RNAs (circRNAs)
  • long non-coding RNAs (lncRNAs)
  • microRNAs (miRNAs)
  • tRNA fragments (tRFs or tiRNAs)
  • transcriptomics
  • cancer pathobiology
  • solid tumors
  • hematological malignancies
  • molecular biomarkers
  • therapeutic targets

Published Papers (2 papers)

2023

Jump to: 2022

13 pages, 1303 KiB  
Article
High Intratumoral i-tRF-GlyGCC Expression Predicts Short-Term Relapse and Poor Overall Survival of Colorectal Cancer Patients, Independent of the TNM Stage
by Spyridon Christodoulou, Katerina Katsaraki, Panteleimon Vassiliu, Nikolaos Danias, Nikolaos Michalopoulos, Georgios Tzikos, Diamantis C. Sideris and Nikolaos Arkadopoulos
Biomedicines 2023, 11(7), 1945; https://doi.org/10.3390/biomedicines11071945 - 8 Jul 2023
Cited by 1 | Viewed by 1198
Abstract
Colorectal cancer (CRC), one of the most prevalent types of cancer, requires the discovery of new tumor biomarkers for accurate patient prognosis. In this work, the prognostic value of the tRNA fragment i-tRF-GlyGCC in CRC was examined. Total RNA extraction from 211 [...] Read more.
Colorectal cancer (CRC), one of the most prevalent types of cancer, requires the discovery of new tumor biomarkers for accurate patient prognosis. In this work, the prognostic value of the tRNA fragment i-tRF-GlyGCC in CRC was examined. Total RNA extraction from 211 CRC patient cancer tissue specimens and 83 adjacent normal tissues was conducted. Each RNA extract was subjected to in vitro polyadenylation and reverse transcription. A real-time quantitative PCR assay was used to quantify i-tRF-GlyGCC in all samples. Extensive biostatics analysis showed that i-tRF-GlyGCC levels in CRC tissues were significantly lower than in matched normal colorectal tissues. Additionally, the disease-free survival (DFS) and overall survival (OS) time intervals were considerably shorter in CRC patients with high i-tRF-GlyGCC expression. i-tRF-GlyGCC expression maintained its prognostic value independently of other established prognostic factors, as shown by the multivariate Cox regression analysis. Additionally, survival analysis after TNM stage stratification revealed that higher i-tRF-GlyGCC levels were linked to shorter DFS time intervals in patients with TNM stage II tumors, as well as an increased probability of having a worse OS for patients in TNM stage II. In conclusion, i-tRF-GlyGCC has the potential to be a useful molecular tissue biomarker in CRC, independent of other clinicopathological variables. Full article
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2022

Jump to: 2023

63 pages, 7850 KiB  
Review
Immunomodulatory Properties of Human Breast Milk: MicroRNA Contents and Potential Epigenetic Effects
by Ma’mon M. Hatmal, Mohammad A. I. Al-Hatamleh, Amin N. Olaimat, Walhan Alshaer, Hanan Hasan, Khaled A. Albakri, Enas Alkhafaji, Nada N. Issa, Murad A. Al-Holy, Salim M. Abderrahman, Atiyeh M. Abdallah and Rohimah Mohamud
Biomedicines 2022, 10(6), 1219; https://doi.org/10.3390/biomedicines10061219 - 24 May 2022
Cited by 20 | Viewed by 10775
Abstract
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a [...] Read more.
Infants who are exclusively breastfed in the first six months of age receive adequate nutrients, achieving optimal immune protection and growth. In addition to the known nutritional components of human breast milk (HBM), i.e., water, carbohydrates, fats and proteins, it is also a rich source of microRNAs, which impact epigenetic mechanisms. This comprehensive work presents an up-to-date overview of the immunomodulatory constituents of HBM, highlighting its content of circulating microRNAs. The epigenetic effects of HBM are discussed, especially those regulated by miRNAs. HBM contains more than 1400 microRNAs. The majority of these microRNAs originate from the lactating gland and are based on the remodeling of cells in the gland during breastfeeding. These miRNAs can affect epigenetic patterns by several mechanisms, including DNA methylation, histone modifications and RNA regulation, which could ultimately result in alterations in gene expressions. Therefore, the unique microRNA profile of HBM, including exosomal microRNAs, is implicated in the regulation of the genes responsible for a variety of immunological and physiological functions, such as FTO, INS, IGF1, NRF2, GLUT1 and FOXP3 genes. Hence, studying the HBM miRNA composition is important for improving the nutritional approaches for pregnancy and infant’s early life and preventing diseases that could occur in the future. Interestingly, the composition of miRNAs in HBM is affected by multiple factors, including diet, environmental and genetic factors. Full article
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