Genes

Editorial

Jump to: Research, Review, Other

3 pages, 195 KiB

Open AccessEditorial

The Landscape of Circulating miRNAs in the Post-Genomic Era

by Fabio Lauria and Giuseppe Iacomino

Genes 2022, 13(1), 94; https://doi.org/10.3390/genes13010094 - 30 Dec 2021

Cited by 4 | Viewed by 1739

Abstract

In the past decade, there has been an epochal change in the way that diseases are investigated and diagnosed [...] Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

Research

Jump to: Editorial, Review, Other

12 pages, 2339 KiB

Open AccessArticle

Circulating miRNA-192 and miR-29a as Disease Progression Biomarkers in Hepatitis C Patients with a Prevalence of HCV Genotype 3

by Amin Ullah, Irshad Ur Rehman, Katharina Ommer, Nadeem Ahmed, Margarete Odenthal, Xiaojie Yu, Jamshaid Ahmad, Tariq Nadeem, Qurban Ali and Bashir Ahmad

Genes 2023, 14(5), 1056; https://doi.org/10.3390/genes14051056 - 8 May 2023

Cited by 3 | Viewed by 1862

Abstract

MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and [...] Read more.

MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and 29a in a patient cohort with a high frequency of HCV genotype-3. A total of 222 HCV blood samples were collected and serum were separated. Patients were classified into mild, moderate, and severe liver injury based on their Child–Turcotte–Pugh CTP score. RNA was isolated from the serum and used for quantitative real-time PCR. The HCV genotype-3 (62%) was the predominant HCV genotype. In HCV patients, the serum miR-192 and miR-29a levels were significantly upregulated in comparison to healthy controls (p = 0.0017 and p = 0.0001, respectively). The progression rate of miR-192 and 29a in the patient group with mild was highly upregulated compared to patients with moderate and severe hepatitis infection. The ROC curve of miR-192 and miR-29a of moderate liver disease had a significant diagnostic performance compared to the other HCV-infected groups. The increase in miR-29a and miR-192 serum levels was even slightly higher in patients with HCV genotype-3 than in non-genotype-3 patients. In conclusion, serum miR-192 and miR-29a levels significantly increased during the progression of chronic HCV infection. The marked upregulation in patients with HCV genotype-3 suggests them as potential biomarkers for hepatic disease, independently of the HCV genotype. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Graphical abstract

17 pages, 1257 KiB

Open AccessArticle

Doxorubicin and Cisplatin Modulate miR-21, miR-106, miR-126, miR-155 and miR-199 Levels in MCF7, MDA-MB-231 and SK-BR-3 Cells That Makes Them Potential Elements of the DNA-Damaging Drug Treatment Response Monitoring in Breast Cancer Cells—A Preliminary Study

by Anna Mizielska, Iga Dziechciowska, Radosław Szczepański, Małgorzata Cisek, Małgorzata Dąbrowska, Jan Ślężak, Izabela Kosmalska, Marta Rymarczyk, Klaudia Wilkowska, Barbara Jacczak, Ewa Totoń, Natalia Lisiak, Przemysław Kopczyński and Błażej Rubiś

Genes 2023, 14(3), 702; https://doi.org/10.3390/genes14030702 - 12 Mar 2023

Cited by 4 | Viewed by 3224

Abstract

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in [...] Read more.

One of the most innovative medical trends is personalized therapy, based on simple and reproducible methods that detect unique features of cancer cells. One of the good prognostic and diagnostic markers may be the miRNA family. Our work aimed to evaluate changes in selected miRNA levels in various breast cancer cell lines (MCF7, MDA-MB-231, SK-BR-3) treated with doxorubicin or cisplatin. The selection was based on literature data regarding the most commonly altered miRNAs in breast cancer (21-3p, 21-5p, 106a-5p, 126-3p, 126-5p, 155-3p, 155-5p, 199b-3p, 199b-5p, 335-3p, 335-5p). qPCR assessment revealed significant differences in the basal levels of some miRNAs in respective cell lines, with the most striking difference in miR-106a-5p, miR-335-5p and miR-335-3p—all of them were lowest in MCF7, while miR-153p was not detected in SK-BR-3. Additionally, different alterations of selected miRNAs were observed depending on the cell line and the drug. However, regardless of these variables, 21-3p/-5p, 106a, 126-3p, 155-3p and 199b-3p miRNAs were shown to respond either to doxorubicin or to cisplatin treatment. These miRNAs seem to be good candidates for markers of breast cancer cell response to doxorubicin or cisplatin. Especially since some earlier reports suggested their role in affecting pathways and expression of genes associated with the DNA-damage response. However, it must be emphasized that the preliminary study shows effects that may be highly related to the applied drug itself and its concentration. Thus, further examination, including human samples, is required. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

25 pages, 2738 KiB

Open AccessArticle

microRNA Expression Profile of Purified Alveolar Epithelial Type II Cells

by Stefan Dehmel, Katharina J. Weiss, Natalia El-Merhie, Jens Callegari, Birte Konrad, Kathrin Mutze, Oliver Eickelberg, Melanie Königshoff and Susanne Krauss-Etschmann

Genes 2022, 13(8), 1420; https://doi.org/10.3390/genes13081420 - 10 Aug 2022

Cited by 2 | Viewed by 2706

Abstract

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs [...] Read more.

Alveolar type II (ATII) cells are essential for the maintenance of the alveolar homeostasis. However, knowledge of the expression of the miRNAs and miRNA-regulated networks which control homeostasis and coordinate diverse functions of murine ATII cells is limited. Therefore, we asked how miRNAs expressed in ATII cells might contribute to the regulation of signaling pathways. We purified “untouched by antibodies” ATII cells using a flow cytometric sorting method with a highly autofluorescent population of lung cells. TaqMan^® miRNA low-density arrays were performed on sorted cells and intersected with miRNA profiles of ATII cells isolated according to a previously published protocol. Of 293 miRNAs expressed in both ATII preparations, 111 showed equal abundances. The target mRNAs of bona fide ATII miRNAs were used for pathway enrichment analysis. This analysis identified nine signaling pathways with known functions in fibrosis and/or epithelial-to-mesenchymal transition (EMT). In particular, a subset of 19 miRNAs was found to target 21 components of the TGF-β signaling pathway. Three of these miRNAs (miR-16-5p, -17-5p and -30c-5p) were down-modulated by TGF-β1 stimulation in human A549 cells, and concomitant up-regulation of associated mRNA targets (BMPR2, JUN, RUNX2) was observed. These results suggest an important role for miRNAs in maintaining the homeostasis of the TGF-β signaling pathway in ATII cells under physiological conditions. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

21 pages, 7461 KiB

Open AccessArticle

Identification of Antitumor miR-30e-5p Controlled Genes; Diagnostic and Prognostic Biomarkers for Head and Neck Squamous Cell Carcinoma

by Chikashi Minemura, Shunichi Asai, Ayaka Koma, Naoko Kikkawa, Mayuko Kato, Atsushi Kasamatsu, Katsuhiro Uzawa, Toyoyuki Hanazawa and Naohiko Seki

Genes 2022, 13(7), 1225; https://doi.org/10.3390/genes13071225 - 9 Jul 2022

Cited by 5 | Viewed by 2557

Abstract

Analysis of microRNA (miRNA) expression signatures in head and neck squamous cell carcinoma (HNSCC) has revealed that the miR-30 family is frequently downregulated in cancer tissues. The Cancer Genome Atlas (TCGA) database confirms that all members of the miR-30 family (except miR-30c-5p) [...] Read more.

Analysis of microRNA (miRNA) expression signatures in head and neck squamous cell carcinoma (HNSCC) has revealed that the miR-30 family is frequently downregulated in cancer tissues. The Cancer Genome Atlas (TCGA) database confirms that all members of the miR-30 family (except miR-30c-5p) are downregulated in HNSCC tissues. Moreover, low expression of miR-30e-5p and miR-30c-1-3p significantly predicts shorter survival of HNSCC patients (p = 0.0081 and p = 0.0224, respectively). In this study, we focused on miR-30e-5p to investigate its tumor-suppressive roles and its control of oncogenic genes in HNSCC cells. Transient expression of miR-30e-5p significantly attenuated cancer cell migration and invasive abilities in HNSCC cells. Nine genes (DDIT4, FOXD1, FXR1, FZD2, HMGB3, MINPP1, PAWR, PFN2, and RTN4R) were identified as putative targets of miR-30e-5p control. Their expression levels significantly predicted shorter survival of HNSCC patients (p < 0.05). Among those targets, FOXD1 expression appeared to be an independent factor predicting patient survival according to multivariate Cox regression analysis (p = 0.049). Knockdown assays using siRNAs corresponding to FOXD1 showed that malignant phenotypes (e.g., cell proliferation, migration, and invasive abilities) of HNSCC cells were significantly suppressed. Overexpression of FOXD1 was confirmed by immunostaining of HNSCC clinical specimens. Our miRNA-based approach is an effective strategy for the identification of prognostic markers and therapeutic target molecules in HNSCC. Moreover, these findings led to insights into the molecular pathogenesis of HNSCC. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

14 pages, 4314 KiB

Open AccessArticle

A Possible Cause for the Differential Expression of a Subset of miRNAs in Mesenchymal Stem Cells Derived from Myometrium and Leiomyoma

by Mariangela Di Vincenzo, Concetta De Quattro, Marzia Rossato, Raffaella Lazzarini, Giovanni Delli Carpini, Andrea Ciavattini and Monia Orciani

Genes 2022, 13(7), 1106; https://doi.org/10.3390/genes13071106 - 21 Jun 2022

Cited by 2 | Viewed by 1580

Abstract

The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, [...] Read more.

The aetiology of leiomyoma is debated; however, dysregulated progenitor cells or miRNAs appear to be involved. Previous profiling analysis of miRNA in healthy myometrium- (M-MSCs) and leiomyoma- (L-MSCs) derived mesenchymal stem cells (MSCs) identified 15 miRNAs differentially expressed between M-MSCs and L-MSCs. Here, we try to elucidate whether these differentially regulated 15 miRNAs arise as a conversion of M-MSCs along the differentiation process or whether they may originate from divergent cell commitment. To trace the origin of the dysregulation, a comparison was made of the expression of miRNAs previously identified as differentially regulated in M-MSCs and L-MSCs with that detected in MSCs from amniotic fluid (considered as a substitute for embryonic cells). The results do not allow for a foregone conclusion: the miRNAs converging to the adherens junction pathway showed a gradual change along the differentiation process, and the miRNAs which coincided with the other three pathways (ECM-receptor interaction, TGFβ and cell cycle) showed a complex, not linear, regulation and, therefore, a trend along the hypothetical differentiation process was not deduced. However, the role of miRNAs appears to be predominant in the onset of leiomyoma and may follow two different mechanisms (early commitment; exacerbation); furthermore, miRNAs can support the observed (epigenetic) predisposition. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

14 pages, 1301 KiB

Open AccessEditor’s ChoiceArticle

miRNAs Copy Number Variations Repertoire as Hallmark Indicator of Cancer Species Predisposition

by Chiara Vischioni, Fabio Bove, Matteo De Chiara, Federica Mandreoli, Riccardo Martoglia, Valentino Pisi, Gianni Liti and Cristian Taccioli

Genes 2022, 13(6), 1046; https://doi.org/10.3390/genes13061046 - 10 Jun 2022

Cited by 6 | Viewed by 3049

Abstract

Aging is one of the hallmarks of multiple human diseases, including cancer. We hypothesized that variations in the number of copies (CNVs) of specific genes may protect some long-living organisms theoretically more susceptible to tumorigenesis from the onset of cancer. Based on the [...] Read more.

Aging is one of the hallmarks of multiple human diseases, including cancer. We hypothesized that variations in the number of copies (CNVs) of specific genes may protect some long-living organisms theoretically more susceptible to tumorigenesis from the onset of cancer. Based on the statistical comparison of gene copy numbers within the genomes of both cancer-prone and -resistant species, we identified novel gene targets linked to tumor predisposition, such as CD52, SAT1 and SUMO. Moreover, considering their genome-wide copy number landscape, we discovered that microRNAs (miRNAs) are among the most significant gene families enriched for cancer progression and predisposition. Through bioinformatics analyses, we identified several alterations in miRNAs copy number patterns, involving miR-221, miR-222, miR-21, miR-372, miR-30b, miR-30d and miR-31, among others. Therefore, our analyses provide the first evidence that an altered miRNAs copy number signature can statistically discriminate species more susceptible to cancer from those that are tumor resistant, paving the way for further investigations. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

9 pages, 278 KiB

Open AccessArticle

Circulating miRNAs Are Associated with Inflammation Biomarkers in Children with Overweight and Obesity: Results of the I.Family Study

by Fabio Lauria, Giuseppe Iacomino, Paola Russo, Antonella Venezia, Pasquale Marena, Wolfgang Ahrens, Stefaan De Henauw, Gabriele Eiben, Ronja Foraita, Antje Hebestreit, Yiannis Kourides, Dénes Molnár, Luis A. Moreno, Toomas Veidebaum and Alfonso Siani

Genes 2022, 13(4), 632; https://doi.org/10.3390/genes13040632 - 1 Apr 2022

Cited by 12 | Viewed by 2789

Abstract

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of [...] Read more.

Increasing data suggest that overnutrition-induced obesity may trigger an inflammatory process in adipose tissue and upturn in the innate immune system. Numerous players have been involved in governing the inflammatory response, including epigenetics. Among epigenetic players, miRNAs are emerging as crucial regulators of immune cell development, immune responses, autoimmunity, and inflammation. In this study, we aimed at identifying the involvement of candidate miRNAs in relation to inflammation-associated biomarkers in a subsample of European children with overweight and obesity participating in the I.Family study. The study sample included individuals with increased adiposity since this condition contributes to the early occurrence of chronic low-grade inflammation. We focused on the acute-phase reagent C-reactive protein (CRP) as the primary outcome and selected cytokines as plausible biomarkers of inflammation. We found that chronic low-grade CRP elevation shows a highly significant association with miR-26b-3p and hsa-miR-576-5p in boys. Furthermore, the association of CRP with hsa-miR-10b-5p and hsa-miR-31-5p is highly significant in girls. We also observed major sex-related associations of candidate miRNAs with selected cytokines. Except for IL-6, a significant association of hsa-miR-26b-3p and hsa-miR-576-5p with TNF-α, IL1-Ra, IL-8, and IL-15 levels was found exclusively in boys. The findings of this exploratory study suggest sex differences in the association of circulating miRNAs with inflammatory response biomarkers, and indicate a possible role of miRNAs among the candidate epigenetic mechanisms related to the process of low-grade inflammation in childhood obesity. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

15 pages, 3211 KiB

Open AccessArticle

Latent Membrane Protein 1 (LMP1) from Epstein–Barr Virus (EBV) Strains M81 and B95.8 Modulate miRNA Expression When Expressed in Immortalized Human Nasopharyngeal Cells

by Barbara G. Müller Coan, Ethel Cesarman, Marcio Luis Acencio and Deilson Elgui de Oliveira

Genes 2022, 13(2), 353; https://doi.org/10.3390/genes13020353 - 16 Feb 2022

Cited by 3 | Viewed by 3248

Abstract

The Epstein–Barr virus (EBV) is a ubiquitous γ herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ [...] Read more.

The Epstein–Barr virus (EBV) is a ubiquitous γ herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ in cell tropism and the activation of the lytic cycle. Nonetheless, it is unknown whether LMP1 from these strains have different effects when expressed in nasopharyngeal cells. Thus, herein we evaluated the effects of EBV LMP1 derived from viral strains B95.8 and M81 and expressed in immortalized nasopharyngeal cells NP69^SV40T in the regulation of 91 selected cellular miRNAs. We found that cells expressing either LMP1 behave similarly in terms of NF-kB activation and cell migration. Nonetheless, the miRs 100-5p, 192-5p, and 574-3p were expressed at higher levels in cells expressing LMP1 B95.8 compared to M81. Additionally, results generated by in silico pathway enrichment analysis indicated that LMP1 M81 distinctly regulate genes involved in cell cycle (i.e., RB1), mRNA processing (i.e., NUP50), and mitochondrial biogenesis (i.e., ATF2). In conclusion, LMP1 M81 was found to distinctively regulate miRs 100-5p, 192-5p, and 574-3p, and the in silico analysis provided valuable clues to dissect the molecular effects of EBV LMP1 expressed in nasopharyngeal cells. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

9 pages, 3260 KiB

Open AccessArticle

MiR-612, miR-637, and miR-874 can Regulate VEGFA Expression in Hepatocellular Carcinoma Cell Lines

by Márcia Maria U. Castanhole-Nunes, Nathalia M. Tunissiolli, André R. C. P. Oliveira, Marlon F. Mattos, Ana Lívia S. Galbiatti-Dias, Rosa S. Kawasaki-Oyama, Erika C. Pavarino, Renato F. da Silva and Eny M. Goloni-Bertollo

Genes 2022, 13(2), 282; https://doi.org/10.3390/genes13020282 - 30 Jan 2022

Cited by 3 | Viewed by 2913

Abstract

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as important posttranscriptional gene and protein expression regulators in cancer. The study goal was to examine VEGFA (vascular endothelial growth factor A) expression in hepatocellular carcinoma (HCC) cell lines upon transfection miR-612, miR-637, or miR-874. [...] Read more.

MicroRNAs (miRNAs) are short non-coding RNA molecules acting as important posttranscriptional gene and protein expression regulators in cancer. The study goal was to examine VEGFA (vascular endothelial growth factor A) expression in hepatocellular carcinoma (HCC) cell lines upon transfection miR-612, miR-637, or miR-874. Methods: MiR-612 mimics, miR-637 mimics, or miR-874 inhibitors were transfected using Lipofectamine RNAiMax in both HCC cell lines, HepG2 and HuH-7. Real-time PCR, Western blotting, and ELISA methods were used to evaluate VEGFA regulation by the miRNAs. Results: Gene and protein expression levels of VEGFA were down-expressed in both cell lines, HepG2 and HuH-7, transfected with miR-612 or miR-637. Transfection with miR-874 inhibitor showed an increase in VEGFA gene expression in HepG2 and HuH-7 cell lines; however, no regulation was observed on VEGFA protein expression by miR-874 inhibition. Correlation analysis between miRNAs and VEGFA protein expression showed that miR-637 and miR-874 expression present inversely correlated to VEGFA protein expression. Conclusions: VEGFA was down-regulated in response to hsa-miR-612 or hsa-miR-637 overexpression; however, the modulation of VEGFA by miR-874 was observed only at the gene expression and thus, needs further investigation. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

12 pages, 1687 KiB

Open AccessArticle

Circulating Transcriptional Profile Modulation in Response to Metabolic Unbalance Due to Long-Term Exercise in Equine Athletes: A Pilot Study

by Katia Cappelli, Samanta Mecocci, Stefano Capomaccio, Francesca Beccati, Andrea Rosario Palumbo, Alessia Tognoloni, Marco Pepe and Elisabetta Chiaradia

Genes 2021, 12(12), 1965; https://doi.org/10.3390/genes12121965 - 9 Dec 2021

Cited by 6 | Viewed by 2630

Abstract

Physical exercise has been associated with the modulation of micro RNAs (miRNAs), actively released in body fluids and recognized as accurate biomarkers. The aim of this study was to measure serum miRNA profiles in 18 horses taking part in endurance competitions, which represents [...] Read more.

Physical exercise has been associated with the modulation of micro RNAs (miRNAs), actively released in body fluids and recognized as accurate biomarkers. The aim of this study was to measure serum miRNA profiles in 18 horses taking part in endurance competitions, which represents a good model to test metabolic responses to moderate intensity prolonged efforts. Serum levels of miRNAs of eight horses that were eliminated due to metabolic unbalance (Non Performer-NP) were compared to those of 10 horses that finished an endurance competition in excellent metabolic condition (Performer-P). Circulating miRNA (ci-miRNA) profiles in serum were analyzed through sequencing, and differential gene expression analysis was assessed comparing NP versus P groups. Target and pathway analysis revealed the up regulation of a set of miRNAs (of mir-211 mir-451, mir-106b, mir-15b, mir-101-1, mir-18a, mir-20a) involved in the modulation of myogenesis, cardiac and skeletal muscle remodeling, angiogenesis, ventricular contractility, and in the regulation of gene expression. Our preliminary data open new scenarios in the definition of metabolic adaptations to the establishment of efficient training programs and the validation of athletes’ elimination from competitions. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research, Other

14 pages, 834 KiB

Open AccessEditor’s ChoiceReview

miRNAs: The Road from Bench to Bedside

by Giuseppe Iacomino

Genes 2023, 14(2), 314; https://doi.org/10.3390/genes14020314 - 25 Jan 2023

Cited by 30 | Viewed by 6796

Abstract

miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids [...] Read more.

miRNAs are small noncoding RNAs that control gene expression at the posttranscriptional level. It has been recognised that miRNA dysregulation reflects the state and function of cells and tissues, contributing to their dysfunction. The identification of hundreds of extracellular miRNAs in biological fluids has underscored their potential in the field of biomarker research. In addition, the therapeutic potential of miRNAs is receiving increasing attention in numerous conditions. On the other hand, many operative problems including stability, delivery systems, and bioavailability, still need to be solved. In this dynamic field, biopharmaceutical companies are increasingly engaged, and ongoing clinical trials point to anti-miR and miR-mimic molecules as an innovative class of molecules for upcoming therapeutic applications. This article aims to provide a comprehensive overview of current knowledge on several pending issues and new opportunities offered by miRNAs in the treatment of diseases and as early diagnostic tools in next-generation medicine. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

24 pages, 3072 KiB

Open AccessReview

Emerging Roles and Potential Applications of Non-Coding RNAs in Cervical Cancer

by Deepak Parashar, Anupam Singh, Saurabh Gupta, Aishwarya Sharma, Manish K. Sharma, Kuldeep K. Roy, Subhash C. Chauhan and Vivek K. Kashyap

Genes 2022, 13(7), 1254; https://doi.org/10.3390/genes13071254 - 15 Jul 2022

Cited by 15 | Viewed by 4155

Abstract

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current [...] Read more.

Cervical cancer (CC) is a preventable disease using proven interventions, specifically prophylactic vaccination, pervasive disease screening, and treatment, but it is still the most frequently diagnosed cancer in women worldwide. Patients with advanced or metastatic CC have a very dismal prognosis and current therapeutic options are very limited. Therefore, understanding the mechanism of metastasis and discovering new therapeutic targets are crucial. New sequencing tools have given a full visualization of the human transcriptome’s composition. Non-coding RNAs (NcRNAs) perform various functions in transcriptional, translational, and post-translational processes through their interactions with proteins, RNA, and even DNA. It has been suggested that ncRNAs act as key regulators of a variety of biological processes, with their expression being tightly controlled under physiological settings. In recent years, and notably in the past decade, significant effort has been made to examine the role of ncRNAs in a variety of human diseases, including cancer. Therefore, shedding light on the functions of ncRNA will aid in our better understanding of CC. In this review, we summarize the emerging roles of ncRNAs in progression, metastasis, therapeutics, chemo-resistance, human papillomavirus (HPV) regulation, metabolic reprogramming, diagnosis, and as a prognostic biomarker of CC. We also discussed the role of ncRNA in the tumor microenvironment and tumor immunology, including cancer stem cells (CSCs) in CC. We also address contemporary technologies such as antisense oligonucleotides, CRISPR–Cas9, and exosomes, as well as their potential applications in targeting ncRNAs to manage CC. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

11 pages, 659 KiB

Open AccessReview

Circulating microRNAs as the Potential Diagnostic and Prognostic Biomarkers for Nasopharyngeal Carcinoma

by Thuy Ai Huyen Le and Thuan Duc Lao

Genes 2022, 13(7), 1160; https://doi.org/10.3390/genes13071160 - 27 Jun 2022

Cited by 4 | Viewed by 2154

Abstract

microRNAs are endogenous non-coding miRNAs, 19–25 nucleotides in length, that can be detected in the extracellular environment in stable forms, named circulating miRNAs (CIR-miRNAs). Since the first discovery of CIR-miRNAs, a large number of studies have demonstrated that the abnormal changes in its [...] Read more.

microRNAs are endogenous non-coding miRNAs, 19–25 nucleotides in length, that can be detected in the extracellular environment in stable forms, named circulating miRNAs (CIR-miRNAs). Since the first discovery of CIR-miRNAs, a large number of studies have demonstrated that the abnormal changes in its expression could be used to significantly distinguish nasopharyngeal carcinoma (NPC) from healthy cells. We herein reviewed and highlighted recent advances in the study of CIR-miRNAs in NPC, which pointed out the main components serving as promising and effective biomarkers for NPC diagnosis and prognosis. Furthermore, brief descriptions of its origin and unique characteristics are provided. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

12 pages, 1051 KiB

Open AccessEditor’s ChoiceReview

Considerations and Suggestions for the Reliable Analysis of miRNA in Plasma Using qRT-PCR

by Eunmi Ban and Eun Joo Song

Genes 2022, 13(2), 328; https://doi.org/10.3390/genes13020328 - 10 Feb 2022

Cited by 38 | Viewed by 5732

Abstract

MicroRNAs (miRNAs) are promising molecules that can regulate gene expression, and their expression level and type have been associated with early diagnosis, targeted therapy, and prognosis of various diseases. Therefore, analysis of miRNA in the plasma or serum is useful for the discovery [...] Read more.

MicroRNAs (miRNAs) are promising molecules that can regulate gene expression, and their expression level and type have been associated with early diagnosis, targeted therapy, and prognosis of various diseases. Therefore, analysis of miRNA in the plasma or serum is useful for the discovery of biomarkers and the diagnosis of implicated diseases to achieve potentially unprecedented progress in early treatment. Numerous methods to improve sensitivity have recently been proposed and confirmed to be valuable in miRNA detection. Specifically, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) is an effective and common method for sensitive and specific analysis of miRNA from biological fluids, such as plasma or serum. Despite this, the application of qRT-PCR is limited, as it can be affected by various contaminants. Therefore, extraction studies have been frequently conducted to maximize the extracted miRNA amount while simultaneously minimizing contaminants. Moreover, studies have evaluated extraction efficiency and normalization of the extracted sample. However, variability in results among laboratories still exists. In this review, we aimed to summarize the factors influencing the qualification and quantification of miRNAs in the plasma using qRT-PCR. Factors influencing reliable analysis of miRNA using qRT-PCR are described in detail. Additionally, we aimed to describe the importance of evaluating extraction and normalization for reliable miRNA analysis and to explore how miRNA detection accuracy, especially from plasma, can be improved. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

Other

Jump to: Editorial, Research, Review

12 pages, 804 KiB

Open AccessProtocol

Molecular Investigation of miRNA Biomarkers as Chemoresistance Regulators in Melanoma: A Protocol for Systematic Review and Meta-Analysis

by Peter Shaw, Greg Raymond, Katherine S. Tzou, Siddhartha Baxi, Ravishankar Ram Mani, Suresh Kumar Govind, Harish C. Chandramoorthy, Palanisamy Sivanandy, Mogana Rajagopal, Suja Samiappan, Sunil Krishnan and Rama Jayaraj

Genes 2022, 13(1), 115; https://doi.org/10.3390/genes13010115 - 8 Jan 2022

Cited by 2 | Viewed by 2899

Abstract

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for [...] Read more.

Introduction: Melanoma is a global disease that is predominant in Western countries. However, reliable data resources and comprehensive studies on the theragnostic efficiency of miRNAs in melanoma are scarce. Hence, a decisive study or comprehensive review is required to collate the evidence for profiling miRNAs as a theragnostic marker. This protocol details a comprehensive systematic review and meta-analysis on the impact of miRNAs on chemoresistance and their association with theragnosis in melanoma. Methods and analysis: The articles will be retrieved from online bibliographic databases, including Cochrane Review, EMBASE, MEDLINE, PubMed, Scopus, Science Direct, and Web of Science, with different permutations of ‘keywords’. To obtain full-text papers of relevant research, a stated search method will be used, along with selection criteria. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Protocols 2015 (PRISMA-P) standards were used to create this study protocol. The hazard ratio (HR) with a 95% confidence interval will be analyzed using Comprehensive Meta-Analysis (CMA) software 3.0. (CI). The pooled effect size will be calculated using a random or fixed-effects meta-analysis model. Cochran’s Q test and the I2 statistic will be used to determine heterogeneity. Egger’s bias indicator test, Orwin’s and the classic fail-safe N tests, the Begg and Mazumdar rank collection test, and Duval and Tweedie’s trim and fill calculation will all be used to determine publication bias. The overall standard deviation will be evaluated using Z-statistics. Subgroup analyses will be performed according to the melanoma participants’ clinicopathological and biological characteristics and methodological factors if sufficient studies and retrieved data are identified and available. The source of heterogeneity will be assessed using a meta-regression analysis. A pairwise matrix could be developed using either a pairwise correlation or expression associations of miRNA with patients’ survival for the same studies. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

10 pages, 654 KiB

Open AccessProtocol

Clinical Theragnostic Relationship between Chemotherapeutic Resistance, and Sensitivity and miRNA Expressions in Head and Neck Cancers: A Systematic Review and Meta-Analysis Protocol

by Peter Shaw, Greg Raymond, Raghul Senthilnathan, Chellan Kumarasamy, Siddhartha Baxi, Deepa Suresh, Sameep Shetty, Ravishankar Ram M, Harish C. Chandramoorthy, Palanisamy Sivanandy, Suja Samiappan, Mogana Rajagopal, Sunil Krishnan and Rama Jayaraj

Genes 2021, 12(12), 2029; https://doi.org/10.3390/genes12122029 - 20 Dec 2021

Cited by 4 | Viewed by 3805

Abstract

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19–25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental [...] Read more.

Background: The microRNAs (miRNAs) are small noncoding single-stranded RNAs typically 19–25 nucleotides long and regulated by cellular and epigenetic factors. These miRNAs plays important part in several pathways necessary for cancer development, an altered miRNA expression can be oncogenic or tumor-suppressive. Recent experimental results on miRNA have illuminated a different perspective of the molecular pathogenesis of head and neck cancers. Regulation of miRNA can have a detrimental effect on the efficacy of chemotherapeutic drugs in both neoadjuvant and adjuvant settings. This miRNA-induced chemoresistance can influence the prognosis and survival rate. The focus of the study is on how regulations of various miRNA levels contribute to chemoresistance in head and neck cancer (HNC). Recent findings suggest that up or down-regulation of miRNAs may lead to resistance towards various chemotherapeutic drugs, which may influence the prognosis. Methods: Studies on miRNA-specific chemoresistance in HNC were collected through literary (bibliographic) databases, including SCOPUS, PubMed, Nature, Elsevier, etc., and were systematically reviewed following PRISMA-P guidelines (Preferred Reporting Items for Systematic Review and Meta-analysis Protocol). We evaluated various miRNAs, their up and downregulation, the effect of altered regulation on the patient’s prognosis, resistant cell lines, etc. The data evaluated will be represented in the form of a review and meta-analysis. Discussion: This meta-analysis aims to explore the miRNA-induced chemoresistance in HNC and thus to aid further researches on this topic. PROSPERO registration: CRD42018104657. Full article

(This article belongs to the Special Issue The Ins and Outs of miRNAs as Biomarkers)

► Show Figures

Figure 1

Journal Menu

Journal Browser

The Ins and Outs of miRNAs as Biomarkers

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Related Special Issue

Published Papers (17 papers)

Editorial

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI