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The Role of Non‐coding RNAs in Human Health and Diseases
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The Role of Non‐coding RNAs in Human Health and Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 April 2025 | Viewed by 11164

Special Issue Editor

Dr. Bertrand Kaeffer

E-Mail Website
Guest Editor
UMR-1280, INRA, University of Nantes, Physiologie des Adaptations Nutritionnelles, 44093 Nantes, France
Interests: miRNA; lncRNA; mRNA; genome stability; perinatal; fetus; baby; circadian clock; aging; cell cycle regulation; reproduction; transgenerational epigenetic inheritance

Special Issue Information

Dear Colleagues,

Non-coding RNAs finely tune epigenetic mechanisms, allowing for the maintenance of organism homeostasis from fecundation to old age. Homeostasis is the capacity of a living structure to not only withstand and adapt its internal conditions to progressive or sudden changes in the environment but also to anticipate the occurrence of reoccurring events (i.e., reactive homeostasis including circadian rhythms). Maintenance of the cellular phenotype is dependent on molecular epigenetics, and the integration of molecular networks at the organism level is partly driven by non-coding RNAs.

This Special Issue of IJMS will address these mechanisms maintaining the memory of cellular phenotypes, with a particular focus on non-coding RNAs. We welcome the submission of full reviews, original research papers, and short communications, as well as perspectives concerning the above-mentioned mechanisms.

Dr. Bertrand Kaeffer
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • miRNA
  • lncRNA
  • mRNA
  • genome stability
  • perinatal
  • fetus
  • baby
  • circadian clock
  • aging
  • cell cycle regulation
  • reproduction
  • transgenerational epigenetic inheritance

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Published Papers (6 papers)

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Research

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12 pages, 2111 KiB  
Article
The Functional Role of the Long Non-Coding RNA LINCMD1 in Leiomyoma Pathogenesis
by Tsai-Der Chuang, Nhu Ton, Shawn Rysling and Omid Khorram
Int. J. Mol. Sci. 2024, 25(21), 11539; https://doi.org/10.3390/ijms252111539 - 27 Oct 2024
Viewed by 563
Abstract
Existing evidence indicates that LINCMD1 regulates muscle differentiation-related gene expression in skeletal muscle by acting as a miRNA sponge, though its role in leiomyoma development is still unknown. This study investigated LINCMD1′s involvement in leiomyoma by analyzing paired myometrium and leiomyoma tissue samples [...] Read more.
Existing evidence indicates that LINCMD1 regulates muscle differentiation-related gene expression in skeletal muscle by acting as a miRNA sponge, though its role in leiomyoma development is still unknown. This study investigated LINCMD1′s involvement in leiomyoma by analyzing paired myometrium and leiomyoma tissue samples (n = 34) from patients who had not received hormonal treatments for at least three months prior to surgery. Myometrium smooth muscle cells (MSMCs) were isolated, and gene expression of LINCMD1 and miR-135b was assessed via qRT-PCR, while luciferase assays determined the interaction between LINCMD1 and miR-135b. To examine the effects of LINCMD1 knockdown, siRNA transfection was applied to a 3D MSMC spheroid culture, followed by qRT-PCR and Western blot analyses of miR-135b, APC, β-Catenin and COL1A1 expression. The results showed that leiomyoma tissues had significantly reduced LINCMD1 mRNA levels, regardless of patient race or MED12 mutation status, while miR-135b levels were elevated compared to matched myometrium samples. Luciferase assays confirmed LINCMD1′s role as a sponge for miR-135b. LINCMD1 knockdown in MSMC spheroids increased miR-135b levels, reduced APC expression, and led to β-Catenin accumulation and higher COL1A1 expression. These findings highlight LINCMD1 as a potential therapeutic target to modulate aberrant Wnt/β-Catenin signaling in leiomyoma. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
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17 pages, 8934 KiB  
Article
Identification of Tumor Suppressive miR-144-5p Targets: FAM111B Expression Accelerates the Malignant Phenotypes of Lung Adenocarcinoma
by Yuya Tomioka, Naohiko Seki, Takayuki Suetsugu, Yoko Hagihara, Hiroki Sanada, Yusuke Goto, Naoko Kikkawa, Keiko Mizuno, Kentaro Tanaka and Hiromasa Inoue
Int. J. Mol. Sci. 2024, 25(18), 9974; https://doi.org/10.3390/ijms25189974 - 16 Sep 2024
Viewed by 702
Abstract
Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that miR-144-5p (the passenger strand derived from [...] Read more.
Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that miR-144-5p (the passenger strand derived from pre-miR-144) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by miR-144-5p in LUAD cells. Ectopic expression assays demonstrated that miR-144-5p attenuated LUAD cell aggressiveness, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. A total of 18 genes were identified as putative cancer-promoting genes controlled by miR-144-5p in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B (FAM111B) and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of FAM111B was directly regulated by miR-144-5p in LUAD cells. FAM111B knockdown assays showed that LUAD cells significantly suppressed malignant phenotypes, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. Furthermore, we investigated the FAM111B-mediated molecular networks in LUAD cells. Identifying target genes regulated by passenger strands of miRNAs may aid in the discovery of diagnostic markers and therapeutic targets for LUAD. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
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26 pages, 3529 KiB  
Article
MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway
by Seidy Y. Aguilar-Martínez, Gabriela E. Campos-Viguri, Selma E. Medina-García, Ricardo J. García-Flores, Jessica Deas, Claudia Gómez-Cerón, Abraham Pedroza-Torres, Elizabeth Bautista-Rodríguez, Gloria Fernández-Tilapa, Mauricio Rodríguez-Dorantes, Carlos Pérez-Plasencia and Oscar Peralta-Zaragoza
Int. J. Mol. Sci. 2024, 25(7), 4086; https://doi.org/10.3390/ijms25074086 - 6 Apr 2024
Cited by 1 | Viewed by 1867
Abstract
Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In [...] Read more.
Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
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17 pages, 3960 KiB  
Article
Analysis of MicroRNA-Transcription Factors Co-Regulatory Network Linking Depression and Vitamin D Deficiency
by Maria Sala-Cirtog and Ioan-Ovidiu Sirbu
Int. J. Mol. Sci. 2024, 25(2), 1114; https://doi.org/10.3390/ijms25021114 - 17 Jan 2024
Viewed by 1712
Abstract
Depression and vitamin D deficiency are often co-occurring pathologies, the common pathogenetic ground of which includes an augmented inflammatory response. However, the molecular details of this relationship remain unclear. Here, we used a bioinformatic approach to analyze GEO transcriptome datasets of major depressive [...] Read more.
Depression and vitamin D deficiency are often co-occurring pathologies, the common pathogenetic ground of which includes an augmented inflammatory response. However, the molecular details of this relationship remain unclear. Here, we used a bioinformatic approach to analyze GEO transcriptome datasets of major depressive disorder (MDD) and vitamin D deficiency (VDD) to identify the hub genes within the regulatory networks of commonly differentially expressed genes (DEGs). The MDD-VDD shared regulatory network contains 100 DEGs (71 upregulated and 29 downregulated), with six hub genes (PECAM1, TLR2, PTGS2, LRRK2, HCK, and IL18) all significantly upregulated, of which PTGS2 (also known as COX2) shows the highest inference score and reference count. The subsequent analysis of the miRNA-transcription factors network identified COX2, miR-146a-5p, and miR-181c-5p as key co-regulatory actors in the MDD-VDD shared molecular pathogenic mechanisms. Subsequent analysis of published MDD and VDD transcriptome data confirmed the importance of the identified hub genes, further validating our bioinformatic analytical pipeline. Our study demonstrated that PTGS2 was highly upregulated in both depressive patients and patients with low vitamin D plasma levels. Therefore, regulators targeting PTGS2, like miR-146a-5p and miR181c-5p, may have great potential in controlling both diseases simultaneously, accentuating their role in future research. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
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Review

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18 pages, 300 KiB  
Review
MicroRNAs in Pancreatic Cancer: Advances in Biomarker Discovery and Therapeutic Implications
by Roland Madadjim, Thuy An and Juan Cui
Int. J. Mol. Sci. 2024, 25(7), 3914; https://doi.org/10.3390/ijms25073914 - 31 Mar 2024
Cited by 3 | Viewed by 2495
Abstract
Pancreatic cancer remains a formidable malignancy characterized by high mortality rates, primarily attributable to late-stage diagnosis and a dearth of effective therapeutic interventions. The identification of reliable biomarkers holds paramount importance in enhancing early detection, prognostic evaluation, and targeted treatment modalities. Small non-coding [...] Read more.
Pancreatic cancer remains a formidable malignancy characterized by high mortality rates, primarily attributable to late-stage diagnosis and a dearth of effective therapeutic interventions. The identification of reliable biomarkers holds paramount importance in enhancing early detection, prognostic evaluation, and targeted treatment modalities. Small non-coding RNAs, particularly microRNAs, have emerged as promising candidates for pancreatic cancer biomarkers in recent years. In this review, we delve into the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. Drawing upon the latest research advancements in omics data-driven biomarker discovery, we also perform a case study using public datasets and address commonly identified research discrepancies, challenges, and limitations. Lastly, we discuss analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, presenting new insights into identifying robust miRNA-centric biomarkers. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
13 pages, 1833 KiB  
Review
Human Breast Milk miRNAs: Their Diversity and Potential for Preventive Strategies in Nutritional Therapy
by Bertrand Kaeffer
Int. J. Mol. Sci. 2023, 24(22), 16106; https://doi.org/10.3390/ijms242216106 - 9 Nov 2023
Cited by 2 | Viewed by 2507
Abstract
The endogenous miRNAs of breast milk are the products of more than 1000 nonprotein-coding genes, giving rise to mature small regulatory molecules of 19–25 nucleotides. They are incorporated in macromolecular complexes, loaded on Argonaute proteins, sequestrated in exosomes and lipid complexes, or present [...] Read more.
The endogenous miRNAs of breast milk are the products of more than 1000 nonprotein-coding genes, giving rise to mature small regulatory molecules of 19–25 nucleotides. They are incorporated in macromolecular complexes, loaded on Argonaute proteins, sequestrated in exosomes and lipid complexes, or present in exfoliated cells of epithelial, endothelial, or immune origins. Their expression is dependent on the stage of lactation; however, their detection depends on progress in RNA sequencing and the reappraisal of the definition of small RNAs. Some miRNAs from plants are detected in breast milk, opening the possibility of the stimulation of immune cells from the allergy repertoire. Each miRNA harbors a seeding sequence, which targets mRNAs, gene promoters, or long noncoding RNAs. Their activities depend on their bioavailability. Efficient doses of miRNAs are estimated to be roughly 100 molecules in the cytoplasm of target cells from in vitro and in vivo experiments. Each miRNA is included in networks of stimulation/inhibition/sequestration, driving the expression of cellular phenotypes. Three types of stress applied during lactation to manipulate miRNA supply were explored using rodent offspring: a foster mother, a cafeteria diet, and early weaning. This review presents the main mature miRNAs described from current mothers’ cohorts and their bioavailability in experimental models as well as studies assessing the potential of miR-26 or miR-320 miRNA families to alter offspring phenotypes. Full article
(This article belongs to the Special Issue The Role of Non‐coding RNAs in Human Health and Diseases)
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