Non-Coding RNA

8 pages, 253 KiB

Open AccessEditorial

The 2024 Nobel Prize in Physiology or Medicine: microRNA Takes Center Stage

by George A. Calin, Florent Hubé, Michael R. Ladomery, Nicholas Delihas, Manuela Ferracin, Laura Poliseno, Luca Agnelli, Suresh K. Alahari, Ai-Ming Yu and Xiao-Bo Zhong

Non-Coding RNA 2024, 10(6), 62; https://doi.org/10.3390/ncrna10060062 - 12 Dec 2024

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Abstract

The Non-coding Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering [...] Read more.

The Non-coding Journal Editorial Board Members would like to congratulate Victor Ambros and Gary Ruvkun, who were jointly awarded the 2024 Nobel Prize in Physiology or Medicine for their groundbreaking discovery of microRNAs and the role of microRNAs in post-transcriptional gene regulation, uncovering a previously unknown layer of gene control in eukaryotes [...] Full article

12 pages, 885 KiB

Open AccessArticle

Urinary miRNA Expression in Pre-Eclampsia During Early and Mid-Pregnancy

by Roman A. Illarionov, Anastasia R. Maltseva, Olga V. Pachuliia, Tatiana B. Postnikova, Elena S. Vashukova, Anastasiia K. Popova, Yulia A. Nasykhova, Olesya N. Bespalova and Andrey S. Glotov

Non-Coding RNA 2024, 10(6), 61; https://doi.org/10.3390/ncrna10060061 - 2 Dec 2024

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Abstract

Background: Pre-eclampsia (PE) is a serious condition affecting 2–8% of pregnancies worldwide, leading to high maternal and fetal morbidity and mortality. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as potential biomarkers for various pregnancy-related pathologies, including PE. MiRNAs in plasma and serum [...] Read more.

Background: Pre-eclampsia (PE) is a serious condition affecting 2–8% of pregnancies worldwide, leading to high maternal and fetal morbidity and mortality. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as potential biomarkers for various pregnancy-related pathologies, including PE. MiRNAs in plasma and serum have been extensively studied, but urinary miRNAs remain underexplored, especially during early pregnancy. This study aimed to investigate the urinary miRNA expression profiles in women with pre-eclampsia during the first and second trimesters. Materials and Methods: A prospective study was conducted using 48 urine samples from 24 pregnant women (n = 12 pre-eclampsia and n = 12 controls). Urine samples were collected in the first (9–13 weeks) and second (22–24 weeks) trimesters. MiRNA isolation, library preparation, and high-throughput sequencing were performed, followed by differential expression and enrichment analyses. Results: In the first trimester, five miRNAs were dysregulated in PE in comparison with the control group (hsa-miR-184, hsa-miR-203a-3p, hsa-miR-205-5p, hsa-miR-223-3p—downregulated; hsa-miR-1-3p—upregulated). In the second trimester, hsa-miR-205-5p and hsa-miR-223-3p were downregulated, and hsa-miR-9-5p, hsa-miR-1-3p, and hsa-miR-206 were upregulated. Conclusions: Our study identified differentially expressed miRNAs in the urine of pre-eclamptic patients during early pregnancy. These findings suggest that specific urinary miRNAs could serve as non-invasive biomarkers for the early detection and risk assessment of pre-eclampsia. The changes in the level of differential expression of miRNAs during gestation highlight their role in the progression of PE. Further research and validation with a larger cohort are needed to explore their clinical potential for improving maternal and fetal outcomes through early intervention. Full article

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15 pages, 4653 KiB

Open AccessArticle

Identification of Tumor-Suppressive miR-30a-3p Controlled Genes: ANLN as a Therapeutic Target in Breast Cancer

by Reiko Mitsueda, Ayako Nagata, Hiroko Toda, Yuya Tomioka, Ryutaro Yasudome, Mayuko Kato, Yoshiaki Shinden, Akihiro Nakajo and Naohiko Seki

Non-Coding RNA 2024, 10(6), 60; https://doi.org/10.3390/ncrna10060060 - 30 Nov 2024

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Abstract

Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some miR-30 family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the miR-30 family members, miR-30a-3p (the passenger strand derived [...] Read more.

Our recently created RNA-sequence-based microRNA (miRNA) expression signature in breast cancer clinical specimens revealed that some miR-30 family members were significantly downregulated in cancer tissues. Based on TCGA database analyses, we observed that among the miR-30 family members, miR-30a-3p (the passenger strand derived from pre-miR-30a) was significantly downregulated in breast cancer (BC) clinical specimens, and its low expression predicted worse prognoses. Ectopic expression assays showed that miR-30a-3p transfected cancer cells (MDA-MB-157 and MDA-MB-231) had their aggressive phenotypes significantly suppressed, e.g., their proliferation, migration, and invasion abilities. These data indicated that miR-30a-3p acted as a tumor-suppressive miRNA in BC cells. Our subsequent search for miR-30a-3p controlled molecular networks in BC cells yielded a total of 189 genes. Notably, among those 189 genes, cell-cycle-related genes (ANLN, MKI67, CCNB1, NCAPG, ZWINT, E2F7, PDS5A, RIF1, BIRC5, MAD2L1, CACUL1, KIF23, UBE2S, EML4, SEPT10, CLTC, and PCNP) were enriched according to a GeneCodis 4 database analysis. Moreover, the overexpression of four genes (ANLN, CCNB1, BIRC5, and KIF23) significantly predicted worse prognoses for patients with BC according to TCGA analyses. Finally, our assays demonstrated that the overexpression of ANLN had cancer-promoting functions in BC cells. The involvement of miR-30a-3p (the passenger strand) in BC molecular pathogenesis is a new concept in cancer research, and the outcomes of our study strongly indicate the importance of analyzing passenger strands of miRNAs in BC cells. Full article

(This article belongs to the Special Issue Non-coding RNA as Biomarker in Cancer)

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12 pages, 1577 KiB

Open AccessReview

SVALKA: A Long Noncoding Cis-Natural Antisense RNA That Plays a Role in the Regulation of the Cold Response of Arabidopsis thaliana

by Nicholas M. Kiger and Susan J. Schroeder

Non-Coding RNA 2024, 10(6), 59; https://doi.org/10.3390/ncrna10060059 - 28 Nov 2024

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Abstract

RNA plays important roles in the regulation of gene expression in response to environmental stimuli. SVALKA, a long noncoding cis-natural antisense RNA, is a key component of regulating the response to cold temperature in Arabidopsis thaliana. There are three mechanisms through [...] Read more.

RNA plays important roles in the regulation of gene expression in response to environmental stimuli. SVALKA, a long noncoding cis-natural antisense RNA, is a key component of regulating the response to cold temperature in Arabidopsis thaliana. There are three mechanisms through which SVALKA fine tunes the transcriptional response to cold temperatures. SVALKA regulates the expression of the CBF1 (C-Repeat Dehydration Binding Factor 1) transcription factor through a collisional transcription mechanism and a dsRNA and DICER mediated mechanism. SVALKA also interacts with Polycomb Repressor Complex 2 to regulate the histone methylation of CBF3. Both CBF1 and CBF3 are key components of the COLD REGULATED (COR) regulon that direct the plant’s response to cold temperature over time, as well as plant drought adaptation, pathogen responses, and growth regulation. The different isoforms of SVALKA and its potential to form dynamic RNA conformations are important features in regulating a complex gene network in concert with several other noncoding RNA. This review will summarize the three mechanisms through which SVALKA participates in gene regulation, describe the ways that dynamic RNA structures support the function of regulatory noncoding RNA, and explore the potential for improving agricultural genetic engineering with a better understanding of the roles of noncoding RNA. Full article

(This article belongs to the Special Issue Non-Coding RNA and Their Regulatory Roles in Plant)

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10 pages, 5690 KiB

Open AccessArticle

Detection of miR-133a-5p Using a Molecular Beacon Probe for Investigating Postmortem Intervals

by Eun Hye Lee, Mingyoung Jeong, Kwangmin Park, Dong Geon Lee, Eun Ju Lee, Haneul Lee, Ah Yeoung Kim, Jae Won Ahn, Hyun Jun Woo, Sunghyun Kim, Jaewon Lim and Jungho Kim

Non-Coding RNA 2024, 10(6), 58; https://doi.org/10.3390/ncrna10060058 - 26 Nov 2024

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Abstract

Background: When a body is discovered at a crime or murder scene, it is crucial to examine the body and estimate its postmortem interval (PMI). Accurate estimation of PMI is vital for identifying suspects and providing clues to resolve the case. MicroRNAs (miRNAs [...] Read more.

Background: When a body is discovered at a crime or murder scene, it is crucial to examine the body and estimate its postmortem interval (PMI). Accurate estimation of PMI is vital for identifying suspects and providing clues to resolve the case. MicroRNAs (miRNAs or miRs) are small non-coding RNAs that remain relatively stable in the cell nucleus even after death-related changes occur. Objective: This study developed a molecular beacon probe for mmu-miR-133a-5p and assessed its use in mouse muscle tissue at temperatures of 4 °C and 21 °C to estimate the PMI. Methods: A total of 36 healthy adult male BALB/c mice were divided into 9 PMI time points (0, 2, 6, 8, and 10 days) with 3 mice per time point, and they were exposed to 4 °C and 21 °C. Next, the expression pattern of mmu-miR-133a in the skeletal muscle tissue over a 10-day PMI period was analyzed using the developed molecular beacon probe. Results: The molecular beacon (MB) probe was designed for optimal thermodynamic stability with a hairpin structure that opened in the presence of mmu-miR-133a-5p, thus separating the fluorophore from the quencher and resulting in a strong fluorescence signal at 495 nm. Fluorescence intensity increased with mmu-miR-133a-5p concentration from 1 ng/μL to 1000 ng/μL and exhibited a strong correlation (R² = 0.9966) and a detection limit of 1 ng/μL. Subsequently, the expression level of mmu-miR-133a-5p was observed to be stable in mouse skeletal muscle tissue at both 4 °C and 21 °C. Conclusions: This user-friendly assay can complete measurements in just 30 min after RNA extraction and is suitable for point-of-care testing, and it possesses the potential to improve existing complex and time-consuming methods for PMI estimation. Full article

(This article belongs to the Section Detection and Biomarkers of Non-Coding RNA)

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9 pages, 591 KiB

Open AccessCommentary

LNC-ing Genetics in Mitochondrial Disease

by Rick Kamps and Emma Louise Robinson

Non-Coding RNA 2024, 10(6), 57; https://doi.org/10.3390/ncrna10060057 - 15 Nov 2024

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Abstract

Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), [...] Read more.

Primary mitochondrial disease (MD) is a group of rare genetic diseases reported to have a prevalence of 1:5000 and is currently without a cure. This group of diseases includes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), Leber’s hereditary optic neuropathy (LHON), Leigh syndrome (LS), Kearns–Sayre syndrome (KSS), and myoclonic epilepsy and ragged-red fiber disease (MERRF). Additionally, secondary mitochondrial dysfunction has been implicated in the most common current causes of mortality and morbidity, including cardiovascular disease (CVD) and cancer. Identifying key genetic contributors to both MD and secondary mitochondrial dysfunction may guide clinicians to assess the most effective treatment course and prognosis, as well as informing family members of any hereditary risk of disease transmission. Identifying underlying genetic causes of primary and secondary MD involves either genome sequencing (GS) or small targeted panel analysis of known disease-causing nuclear- or mitochondrial genes coding for mitochondria-related proteins. Due to advances in GS, the importance of long non-coding RNA (lncRNA) as functional contributors to the pathophysiology of MD is being unveiled. A limited number of studies have thus far reported the importance of lncRNAs in relation to MD causation and progression, and we are entering a new area of attention for clinical geneticists in specific rare malignancies. This commentary provides an overview of what is known about the role of lncRNAs as genetic and molecular contributors to disease pathophysiology and highlights an unmet need for a deeper understanding of mitochondrial dysfunction in serious human disease burdens. Full article

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15 pages, 547 KiB

Open AccessReview

Androgen Receptor and Non-Coding RNAs’ Interaction in Renal Cell Carcinoma

by Manal A. Hussain, Noha M. Elemam and Iman M. Talaat

Non-Coding RNA 2024, 10(6), 56; https://doi.org/10.3390/ncrna10060056 - 12 Nov 2024

Viewed by 851

Abstract

Renal cell carcinoma (RCC), the most prevalent among the urogenital cancers, accounts for around 3% of new cancer cases worldwide. Significantly, the incidence of RCC has doubled in developed world countries, ranking it as the sixth most common cancer in males, who represent [...] Read more.

Renal cell carcinoma (RCC), the most prevalent among the urogenital cancers, accounts for around 3% of new cancer cases worldwide. Significantly, the incidence of RCC has doubled in developed world countries, ranking it as the sixth most common cancer in males, who represent two-thirds of RCC cases. Males with RCC exhibit a higher mortality rate and tend to develop a more aggressive form of the disease than females. Sex-related risk factors, including lifestyle and biological variations, explain this difference. The androgen receptor (AR) oncogenic signaling pathway has been extensively studied among the biological factors that affect RCC. Recent advancements in high-throughput RNA sequencing techniques have underscored the significant roles played by noncoding-RNAs (ncRNAs), previously dismissed as “junk”. The oncogenic potential of AR is manifested through its dysregulation of the ncRNAs’ availability and function, promoting RCC tumorigenesis. This review offers a summary of the most recent findings on the role and molecular mechanisms of the AR in dysregulating the ncRNAs that play a role in the progression of RCC and the possibility of utilizing ncRNAs to target AR as a potential therapeutic strategy. Full article

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16 pages, 3683 KiB

Open AccessArticle

Comparison of Three Computational Tools for the Prediction of RNA Tertiary Structures

by Frank Yiyang Mao, Mei-Juan Tu, Gavin McAllister Traber and Ai-Ming Yu

Non-Coding RNA 2024, 10(6), 55; https://doi.org/10.3390/ncrna10060055 - 8 Nov 2024

Viewed by 966

Abstract

Understanding the structures of noncoding RNAs (ncRNAs) is important for the development of RNA-based therapeutics. There are inherent challenges in employing current experimental techniques to determine the tertiary (3D) structures of RNAs with high complexity and flexibility in folding, which makes computational methods [...] Read more.

Understanding the structures of noncoding RNAs (ncRNAs) is important for the development of RNA-based therapeutics. There are inherent challenges in employing current experimental techniques to determine the tertiary (3D) structures of RNAs with high complexity and flexibility in folding, which makes computational methods indispensable. In this study, we compared the utilities of three advanced computational tools, namely RNAComposer, Rosetta FARFAR2, and the latest AlphaFold 3, to predict the 3D structures of various forms of RNAs, including the small interfering RNA drug, nedosiran, and the novel bioengineered RNA (BioRNA) molecule showing therapeutic potential. Our results showed that, while RNAComposer offered a malachite green aptamer 3D structure closer to its crystal structure, the performances of RNAComposer and Rosetta FARFAR2 largely depend upon the secondary structures inputted, and Rosetta FARFAR2 predictions might not even recapitulate the typical, inverted “L” shape tRNA 3D structure. Overall, AlphaFold 3, integrating molecular dynamics principles into its deep learning framework, directly predicted RNA 3D structures from RNA primary sequence inputs, even accepting several common post-transcriptional modifications, which closely aligned with the experimentally determined structures. However, there were significant discrepancies among three computational tools in predicting the distal loop of human pre-microRNA and larger BioRNA (tRNA fused pre-miRNA) molecules whose 3D structures have not been characterized experimentally. While computational predictions show considerable promise, their notable strengths and limitations emphasize the needs for experimental validation of predictions besides characterization of more RNA 3D structures. Full article

(This article belongs to the Section Computational Biology)

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19 pages, 1428 KiB

Open AccessReview

Extracellular Vesicle lncRNAs as Key Biomolecules for Cell-to-Cell Communication and Circulating Cancer Biomarkers

by Panagiotis Papoutsoglou and Antonin Morillon

Non-Coding RNA 2024, 10(6), 54; https://doi.org/10.3390/ncrna10060054 - 5 Nov 2024

Viewed by 837

Abstract

Extracellular vesicles (EVs) are secreted by almost every cell type and are considered carriers of active biomolecules, such as nucleic acids, proteins, and lipids. Their content can be uptaken and released into the cytoplasm of recipient cells, thereby inducing gene reprogramming and phenotypic [...] Read more.

Extracellular vesicles (EVs) are secreted by almost every cell type and are considered carriers of active biomolecules, such as nucleic acids, proteins, and lipids. Their content can be uptaken and released into the cytoplasm of recipient cells, thereby inducing gene reprogramming and phenotypic changes in the acceptor cells. Whether the effects of EVs on the physiology of recipient cells are mediated by individual biomolecules or the collective outcome of the total transferred EV content is still under debate. The EV RNA content consists of several types of RNA, such as messenger RNA (mRNA), microRNA (miRNA), and long non-coding RNA (lncRNA), the latter defined as transcripts longer than 200 nucleotides that do not code for proteins but have important established biological functions. This review aims to update our insights on the functional roles of EV and their cargo non-coding RNA during cancer progression, to highlight the utility of EV RNA as novel diagnostic or prognostic biomarkers in cancer, and to tackle the technological advances and limitations for EV RNA identification, integrity assessment, and preservation of its functionality. Full article

(This article belongs to the Special Issue Extracellular Vesicles and ncRNA)

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19 pages, 1045 KiB

Open AccessReview

Cardiomyopathies: The Role of Non-Coding RNAs

by Nicole Carabetta, Chiara Siracusa, Isabella Leo, Giuseppe Panuccio, Antonio Strangio, Jolanda Sabatino, Daniele Torella and Salvatore De Rosa

Non-Coding RNA 2024, 10(6), 53; https://doi.org/10.3390/ncrna10060053 - 23 Oct 2024

Viewed by 788

Abstract

Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, [...] Read more.

Cardiomyopathies are the structural and functional disorders of the myocardium. Etiopathogenesis is complex and involves an interplay of genetic, environmental, and lifestyle factors eventually leading to myocardial abnormalities. It is known that non-coding (Nc) RNAs, including micro (mi)-RNAs and long non-coding (lnc) RNAs, play a crucial role in regulating gene expression. Several studies have explored the role of miRNAs in the development of various pathologies, including heart diseases. In this review, we analyzed various patterns of ncRNAs expressed in the most common cardiomyopathies: dilated cardiomyopathy, hypertrophic cardiomyopathy and arrhythmogenic cardiomyopathy. Understanding the role of different ncRNAs implicated in cardiomyopathic processes may contribute to the identification of potential therapeutic targets and novel risk stratification models based on gene expression. The analysis of ncRNAs may also be helpful to unveil the molecular mechanisms subtended to these diseases. Full article

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Non-Coding RNA, Volume 10, Issue 6 (December 2024) – 10 articles

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