Non-coding RNA Regulation of Stem Cell Regenerative Mechanisms: Advances, Challenges, and Perspectives

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (15 October 2023) | Viewed by 4299

Special Issue Editors


E-Mail Website
Guest Editor
Department of Precision and Regenerative Medicine and Ionian Area, University of Bari, Bari, Italy
Interests: regenerative medicine; mesenchymal stem cells; amniotic stem cells tissue engineering; stem cell reparative mechanisms
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Co-Guest Editor
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Interests: clinical nephrology; hemodialysis; kidney transplantation; dialysis; chronic renal failure; transplantation; renal; kidney; chronic kidney failure; peritoneal dialysis; renal disease; kidney disease; fibrosis; transplant immunology and translational research
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The ability to self-renew or differentiate is innate in stem cells (SCs), which are special cells. Through complex signaling networks, both fate decisions are tightly controlled at the molecular level. The function of transcription factors was assumed to be mostly responsible for the regulation of signaling networks promoting self-renewal or differentiation.

In addition, many kinds of non-coding RNA have been demonstrated to have a role in the regulation of stem cell renewal and pluripotency, which in turn affects embryogenesis and development. Among these, the evidence that microRNA and long non-coding RNA are important contributors is very strong. Similar to this, various varieties of non-coding RNA may similarly alter the transcriptional networks that control pluripotency and lineage differentiation.

Circular RNAs, another class of non-coding RNA, have recently been linked to the regulation of human pluripotency. Since they differ from linear RNAs and take on a closed shape, circular RNAs are a subclass of non-coding RNA. It is acknowledged that circular RNA may influence the control of gene expression. According to reports, miRNAs have a higher affinity for binding to circular RNAs than for their natural target mRNA. Circular RNA can therefore act like a sponge to absorb miRNA and lessen their impact on endogenous targets.

However, other regulatory layers with crucial roles in SC fate decisions have emerged, including short noncoding RNAs (ncRNAs), such vault RNAs and their post-transcriptional modifications (the epitranscriptome). New research indicates that short nucleolar RNAs (snoRNAs), particularly in tumor cells, are actively involved in cell proliferation; nevertheless, it is unclear what functions these RNAs play in stem cells.

RNA post-transcriptional changes frequently affect how RNA is recognized, processed, and translated. Through structural changes and specialized RNA-binding proteins (RBPs) known as writers, readers, and erasers, RNA post-transcriptional modifications affect RNA. The epitranscriptome coordinates particular functional tasks via SC-context RBPs. Different strategies are now taking advantage of small ncRNA post-transcriptional alterations to speed up SC translational experiments.

The aim of this Special Issue is to highlight new findings regarding new molecular mechanisms involving non-coding RNA in the regulation of stem cell regenerative properties in order to provide a comprehensive view of advances, challenges, and perspectives in this field.

The topics of this Special Issue will include (but are not limited to) the involvement in SC biology of:

  • Micro RNA;
  • Noncoding RNA;
  • PIWI-interacting RNA
  • Promoter-associated RNA;
  • Small nuclear RNA;
  • Small nucleolar RNA;
  • Vault RNA;
  • Epigenetical regulation in general.

Prof. Dr. Fabio Sallustio
Prof. Dr. Gianluigi Zaza
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 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. Cells 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 2700 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

  • micro RNA
  • noncoding RNA
  • PIWI-interacting RNA
  • promoter-associated RNA
  • small nuclear RNA
  • small nucleolar RNA
  • vault RNA
  • epigenetical regulation in general

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

15 pages, 3085 KiB  
Article
SMYD3 Modulates the HGF/MET Signaling Pathway in Gastric Cancer
by Katia De Marco, Martina Lepore Signorile, Elisabetta Di Nicola, Paola Sanese, Candida Fasano, Giovanna Forte, Vittoria Disciglio, Antonino Pantaleo, Greta Varchi, Alberto Del Rio, Valentina Grossi and Cristiano Simone
Cells 2023, 12(20), 2481; https://doi.org/10.3390/cells12202481 - 18 Oct 2023
Viewed by 1035
Abstract
Gastric cancer (GC) is the third most deadly cancer worldwide. Considerable efforts have been made to find targetable drivers in order to improve patient outcomes. MET is one of the most important factors involved in GC initiation and progression as it plays a [...] Read more.
Gastric cancer (GC) is the third most deadly cancer worldwide. Considerable efforts have been made to find targetable drivers in order to improve patient outcomes. MET is one of the most important factors involved in GC initiation and progression as it plays a major role in GC invasiveness and is related to cancer stemness. Unfortunately, treatment strategies targeting MET are still limited, with a proportion of patients responding to therapy but later developing resistance. Here, we showed that MET is a molecular partner of the SMYD3 methyltransferase in GC cells. Moreover, we found that SMYD3 pharmacological inhibition affects the HGF/MET downstream signaling pathway. Extensive cellular analyses in GC models indicated that EM127, a novel active site-selective covalent SMYD3 inhibitor, can be used as part of a synergistic approach with MET inhibitors in order to enhance the targeting of the HGF/MET pathway. Importantly, our data were confirmed in a 3D GC cell culture system, which was used as a surrogate to evaluate stemness characteristics. Our findings identify SMYD3 as a promising therapeutic target to impair the HGF/MET pathway for the treatment of GC. Full article
Show Figures

Figure 1

16 pages, 6947 KiB  
Article
miR-369-3p Modulates Intestinal Inflammatory Response via BRCC3/NLRP3 Inflammasome Axis
by Viviana Scalavino, Emanuele Piccinno, Anna Maria Valentini, Nicolò Schena, Raffaele Armentano, Gianluigi Giannelli and Grazia Serino
Cells 2023, 12(17), 2184; https://doi.org/10.3390/cells12172184 - 31 Aug 2023
Cited by 2 | Viewed by 1068
Abstract
Inflammasomes are multiprotein complexes expressed by immune cells in response to distinct stimuli that trigger inflammatory responses and the release of pro-inflammatory cytokines. Evidence suggests a different role of inflammasome NLRP3 in IBD. NLRP3 inflammasome activation can be controlled by post-translational modifications such [...] Read more.
Inflammasomes are multiprotein complexes expressed by immune cells in response to distinct stimuli that trigger inflammatory responses and the release of pro-inflammatory cytokines. Evidence suggests a different role of inflammasome NLRP3 in IBD. NLRP3 inflammasome activation can be controlled by post-translational modifications such as ubiquitination through BRCC3. The aim of this study was to investigate the effect of miR-369-3p on the expression and activation of NLRP3 inflammasomes via BRCC3 regulation. After bioinformatics prediction of Brcc3 as a gene target of miR-369-3p, in vitro, we validated its modulation in bone marrow-derived macrophages (BMDM). The increase in miR-369-3p significantly reduced BRCC3 gene and protein expression. This modulation, in turn, reduced the expression of NLRP3 and blocked the recruitment of ASC adaptor protein by NLRP3. As a result, miR-369-3p reduced the activity of Caspase-1 by the inflammasome, decreasing the cleavage of pro-IL-1β and pro-IL-18. These results support a novel mechanism that seems to act on post-translational modification of NLRP3 inflammasome activation by BRCC3. This may be an interesting new target in the personalized treatment of inflammatory disorders, including IBD. Full article
Show Figures

Figure 1

22 pages, 5536 KiB  
Article
Human Adult Renal Progenitor Cells Prevent Cisplatin-Nephrotoxicity by Inducing CYP1B1 Overexpression and miR-27b-3p Down-Regulation through Extracellular Vesicles
by Rossana Franzin, Alessandra Stasi, Giuseppe De Palma, Angela Picerno, Claudia Curci, Serena Sebastiano, Monica Campioni, Antonella Cicirelli, Alessandro Rizzo, Vito Francesco Di Lorenzo, Paola Pontrelli, Giovanni Battista Pertosa, Giuseppe Castellano, Loreto Gesualdo and Fabio Sallustio
Cells 2023, 12(12), 1655; https://doi.org/10.3390/cells12121655 - 17 Jun 2023
Viewed by 1848
Abstract
Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of [...] Read more.
Cisplatin is one of the most effective chemotherapeutic agents strongly associated with nephrotoxicity. Tubular adult renal progenitor cells (tARPC) can regenerate functional tubules and participate in the repair processes after cisplatin exposition. This study investigated the molecular mechanisms underlying the protective effect of tARPC on renal epithelium during cisplatin nephrotoxicity. By performing a whole-genome transcriptomic analysis, we found that tARPC, in presence of cisplatin, can strongly influence the gene expression of renal proximal tubular cell [RPTEC] by inducing overexpression of CYP1B1, a member of the cytochrome P450 superfamily capable of metabolizing cisplatin and of hypoxia/cancer-related lncRNAs as MIR210HG and LINC00511. Particularly, tARPC exerted renoprotection and regeneration effects via extracellular vesicles (EV) enriched with CYP1B1 and miR-27b-3p, a well-known CYP1B1 regulatory miRNA. The expression of CYP1B1 by tARPC was confirmed by analyzing biopsies of cisplatin-treated renal carcinoma patients that showed the colocalization of CYP1B1 with the tARPC marker CD133. CYP1B1 was also overexpressed in urinary EV purified from oncologic patients that presented nephrotoxicity episodes after cisplatin treatment. Interestingly CYP1B1 expression significantly correlated with creatinine and eGFR levels. Taken together, our results show that tARPC are able to counteract cisplatin-induced nephrotoxicity via CYP1B1 release through EV. These findings provide a promising therapeutic strategy for nephrotoxicity risk assessment that could be related to abundance of renal progenitors. Full article
Show Figures

Figure 1

Back to TopTop