-
Frontiers in Genetics 2023With the increasing number of new cancer cases and mortality rates, cancer has become a serious global health problem, but there are no ideal cancer biomarkers for...
With the increasing number of new cancer cases and mortality rates, cancer has become a serious global health problem, but there are no ideal cancer biomarkers for effective diagnosis. Currently, mounting evidence demonstrates that lncRNAs play a fundamental role in cancer progression. BBOX1 anti-sense RNA 1 (BBOX1-AS1) is a recently clarified lncRNA and has been identified as dysregulated in various carcinomas, and it contributes to poor survival in cancer patients. We thoroughly searched six databases for eligible articles published as of 27, April 2023. The association of BBOX1-AS1 expression levels with prognostic and clinicopathological parameters was assessed by odds ratios (OR) and hazard ratios with 95% CIs. Additionally, we further validated our results utilizing the GEPIA online database. Eight studies comprising 602 patients were included in this analysis. High BBOX1-AS1 expression indicated poor overall survival (OS) (hazard ratios = 2.30, 95% Cl [1.99, 2.67], < 0.00001) when compared with low BBOX1-AS1 expression. Furthermore, BBOX1-AS1 expression was positively correlated with lymph node metastasis (OR = 3.00, 95% CI [1.71-5.28], = 0.0001) and advanced tumor stage (OR = 3.74, 95% CI [2.63-5.32], < 0.00001) for cancer patients. Moreover, BBOX1-AS1 was remarkably upregulated in 12 malignancies, and the elevated BBOX1-AS1 expression predicted poorer OS and worse disease-free survival (DFS) confirmed through the GEPIA online gene analysis tool. The findings highlight that BBOX1-AS1 was significantly associated with detrimental overall survival, disease-free survival, lymph node metastasis and tumor stage; thus, it could act as a novel promising biomarker to predict the clinicopathological characteristics and prognosis for various cancers.
PubMed: 37636267
DOI: 10.3389/fgene.2023.1234040 -
Viruses Jul 2023Whether RNA-RNA interactions of cytoplasmic RNA viruses, such as , might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been...
Computational Prediction of RNA-RNA Interactions between Small RNA Tracks from Nonstructural Protein 3 and Neurotrophin Genes during Infection of an Epithelial Lung Cancer Cell Line: Potential Role of Novel Small Regulatory RNA.
Whether RNA-RNA interactions of cytoplasmic RNA viruses, such as , might end in the biogenesis of putative virus-derived small RNAs as miRNA-like molecules has been controversial. Even more, whether RNA-RNA interactions of wild animal viruses may act as virus-derived small RNAs is unknown. Here, we address these issues in four ways. First, we use conserved RNA structures undergoing negative selection in the genomes of SARS-CoV, MERS-CoV, and SARS-CoV-2 circulating in different bat species, intermediate animals, and human hosts. Second, a systematic literature review was conducted to identify -targeting hsa-miRNAs involved in lung cell infection. Third, we employed sophisticated long-range RNA-RNA interactions to refine the seed sequence homology of hsa-miRNAs with conserved RNA structures. Fourth, we used high-throughput RNA sequencing of a -infected epithelial lung cancer cell line (Calu-3) to validate the results. We proposed nine potential virus-derived small RNAs: two vsRNAs in SARS-CoV (Bats: SB-vsRNA-ORF1a-3p; SB-vsRNA-S-5p), one vsRNA in MERS-CoV (Bats: MB-vsRNA-ORF1b-3p), and six vsRNAs in SARS-CoV-2 (Bats: S2B-vsRNA-ORF1a-5p; intermediate animals: S2I-vsRNA-ORF1a-5p; and humans: S2H-vsRNA-ORF1a-5p, S2H-vsRNA-ORF1a-3p, S2H-vsRNA-ORF1b-3p, S2H-vsRNA-ORF3a-3p), mainly encoded by nonstructural protein 3. Notably, -derived small RNAs targeted 74 differentially expressed genes in infected human cells, of which 55 upregulate the molecular mechanisms underlying acute respiratory distress syndrome (ARDS), and the 19 downregulated genes might be implicated in neurotrophin signaling impairment. These results reveal a novel small RNA-based regulatory mechanism involved in neuropathogenesis that must be further studied to validate its therapeutic use.
Topics: Animals; Humans; Chiroptera; SARS-CoV-2; COVID-19; Lung Neoplasms; MicroRNAs; Middle East Respiratory Syndrome Coronavirus; Cell Line; Lung; Nerve Growth Factors
PubMed: 37631989
DOI: 10.3390/v15081647 -
Reproductive Biology and Endocrinology... Aug 2023To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer. (Review)
Review
OBJECTIVE
To systematically identify and narratively synthesize the evidence surrounding liposomal delivery of gene therapy and the outcome for ovarian cancer.
METHODS
An electronic database search of the Embase, MEDLINE and Web of Science from inception until July 7, 2023, was conducted to identify primary studies that investigated the effect of liposomal delivery of gene therapy on ovarian cancer outcomes. Retrieved studies were assessed against the eligibility criteria for inclusion.
RESULTS
The search yielded 564 studies, of which 75 met the inclusion criteria. Four major types of liposomes were identified: cationic, neutral, polymer-coated, and ligand-targeted liposomes. The liposome with the most evidence involved cationic liposomes which are characterized by their positively charged phospholipids (n = 37, 49.3%). Similarly, those with neutrally charged phospholipids, such as 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine, were highly researched as well (n = 25, 33.3%). Eight areas of gene therapy research were identified, evaluating either target proteins/transcripts or molecular pathways: microRNAs, ephrin type-A receptor 2 (EphA2), interleukins, mitogen-activated protein kinase (MAPK), human-telomerase reverse transcriptase/E1A (hTERT/EA1), suicide gene, p53, and multidrug resistance mutation 1 (MDR1).
CONCLUSION
Liposomal delivery of gene therapy for ovarian cancer shows promise in many in vivo studies. Emerging polymer-coated and ligand-targeted liposomes have been gaining interest as they have been shown to have more stability and specificity. We found that gene therapy involving microRNAs was the most frequently studied. Overall, liposomal genetic therapy has been shown to reduce tumor size and weight and improve survivability. More research involving the delivery and targets of gene therapy for ovarian cancer may be a promising avenue to improve patient outcomes.
Topics: Humans; Female; Liposomes; Ligands; MicroRNAs; Phospholipids; Genetic Therapy; Ovarian Neoplasms
PubMed: 37612696
DOI: 10.1186/s12958-023-01125-2 -
International Journal of Molecular... Jul 2023Cholesteatoma is a temporal bone disease characterized by dysfunctions of keratinocytes. MicroRNAs (miRNAs) are evolutionary conserved noncoding RNAs that regulate mRNA... (Review)
Review
Cholesteatoma is a temporal bone disease characterized by dysfunctions of keratinocytes. MicroRNAs (miRNAs) are evolutionary conserved noncoding RNAs that regulate mRNA expression. They can be packaged into exosomes and transported to target cells that can be used in the future therapy of cholesteatoma. This study aimed to collect knowledge on the role of miRNAs and exosomal miRNAs in cholesteatoma and was conducted according to the PRISMA guidelines for systematic reviews. Four databases were screened: Pubmed/MEDLINE, Web of Science, Scopus, and the Cochrane Library. The last search was run on the 6th of June 2023. We included full-text original studies written in English, which examined miRNAs in cholesteatoma. The risk of bias was assessed using the Office of Health Assessment and Translation (OHAT) Risk of Bias Rating Tool, modified for the needs of this review. We identified 118 records and included 18 articles. Analyses revealed the downregulation of exosomal miR-17 as well as miR-10a-5p, miR-125b, miR-142-5p, miR34a, miR-203a, and miR-152-5p and the overexpression of exosomal miR-106b-5p as well as miR-1297, miR-26a-5p, miR-199a, miR-508-3p, miR-21-3p, miR-584-5p, and miR-16-1-3p in cholesteatoma. The role of differentially expressed miRNAs in cholesteatoma, including cell proliferation, apoptosis, the cell cycle, differentiation, bone resorption, and the remodeling process, was confirmed, making them a potential therapeutic target in this disease.
Topics: Humans; MicroRNAs; Cholesteatoma; RNA, Untranslated; Down-Regulation; Keratinocytes; Exosomes
PubMed: 37569652
DOI: 10.3390/ijms241512277 -
Revista Medica Del Instituto Mexicano... Jul 2023Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic... (Review)
Review
Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute's tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.
Topics: Adolescent; Humans; Child; Dental Caries; HLA-DRB1 Chains; Polymorphism, Single Nucleotide; Mannose-Binding Lectin; beta-Defensins; MicroRNAs
PubMed: 37540722
DOI: 10.5281/zenodo.8200501 -
Biomolecules Jun 2023Male infertility is a global health problem that is on the rise. Today, many noncoding RNAs (ncRNAs) are associated with male infertility. Circular RNAs (circRNAs) have... (Review)
Review
Male infertility is a global health problem that is on the rise. Today, many noncoding RNAs (ncRNAs) are associated with male infertility. Circular RNAs (circRNAs) have recently drawn attention, but a comprehensive understanding of the role of circRNAs in male infertility is limited. This systematic review investigates the differential expression of circRNAs in male infertility or circRNAs that could serve as candidate biomarkers. The PRISMA guidelines were used to search PubMed and Web of Science on 11 January 2023. Inclusion criteria were human participants, experimental studies aiming to associate circRNAs with male infertility reporting differentially expressed circRNAs, and the English language. A total of 156 articles were found, and after the screening and eligibility stages, 13 studies were included in the final sample. Many circRNAs are deregulated in male infertility, and their interactions with miRNAs play an important role in affecting cellular processes and pathways. CircRNAs could also be used as biomarkers to screen patients before sperm retrieval. However, most studies focus on the role of circRNAs in azoospermia, and there is a knowledge gap regarding other subtypes of male infertility. Future research is needed to explore the exact mechanism of action of circRNAs and investigate their use as biomarkers.
Topics: Humans; Male; RNA, Circular; Semen; MicroRNAs; Biomarkers; Infertility, Male
PubMed: 37509082
DOI: 10.3390/biom13071046 -
Cells Jul 2023Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and... (Review)
Review
Epigenetic Modifications of MiRNAs in Osteoarthritis: A Systematic Review on Their Methylation Levels and Effects on Chondrocytes, Extracellular Matrix and Joint Inflammation.
Osteoarthritis (OA) is a joint disorder characterized by progressive degeneration of cartilage extracellular matrix (ECM), chondrocyte hypertrophy and apoptosis and inflammation. The current treatments mainly concern pain control and reduction of inflammation, but no therapeutic strategy has been identified as a disease-modifying treatment. Therefore, identifying specific biomarkers useful to prevent, treat or distinguish the stages of OA disease has become an immediate need of clinical practice. The role of microRNAs (miRNAs) in OA has been investigated in the last decade, and increasing evidence has emerged that the influence of the environment on gene expression through epigenetic processes contributes to the development, progression and aggressiveness of OA, in particular acting on the microenvironment modulations. The effects of epigenetic regulation, particularly different miRNA methylation during OA disease, were highlighted in the present systematic review. The evidence arising from this study of the literature conducted in three databases (PubMed, Scopus, Web of Science) suggested that miRNA methylation state already strongly impacts OA progression, driving chondrocytes and synoviocyte proliferation, apoptosis, inflammation and ECM deposition. However, the possibility of understanding the mechanism by which different epigenetic modifications of miRNA or pre-miRNA sequences drive the aggressiveness of OA could be the new focus of future investigations.
Topics: Humans; Chondrocytes; MicroRNAs; Epigenesis, Genetic; Methylation; Osteoarthritis; Inflammation; Extracellular Matrix
PubMed: 37508486
DOI: 10.3390/cells12141821 -
Non-coding RNA Research Dec 2023At present, RNA-based therapy which includes therapies using non-coding RNAs (ncRNAs), antisense oligonucleotides (ASOs), and aptamers are gaining widespread attention... (Review)
Review
At present, RNA-based therapy which includes therapies using non-coding RNAs (ncRNAs), antisense oligonucleotides (ASOs), and aptamers are gaining widespread attention as possible ways to target genes in various cardiovascular diseases (CVDs), thereby serving as a promising therapeutic approach for CVDs and risk factors management. However, data are primarily in an early stage. A systematic review was carried out using literature from several databases (Pubmed, Cochrane, Scopus, and DOAJR) following the PRISMA guidelines. Of the 64 articles reviewed, 39 papers were included in this review with three main types of RNAs: aptamers, antisense oligonucleotides (ASOs), and small-interfering RNA (siRNA). All studies were human clinical trials. RNA-based therapies were demonstrated to be efficacious in treating various CVDs and controlling cardiovascular risk factors. They are generally safe and well-tolerated. However, data are still in the early stage and warrant further investigation.
PubMed: 37483458
DOI: 10.1016/j.ncrna.2023.06.002 -
International Journal of Molecular... Jun 2023MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence... (Review)
Review
MicroRNAs (miRNAs) are emerging as biomarkers for the detection and prognosis of cancers due to their inherent stability and resilience. To summarize the evidence regarding the role of urinary miRNAs (umiRNAs) in the detection, prognosis, and therapy of genitourinary cancers, we performed a systematic review of the most important scientific databases using the following keywords: (urinary miRNA) AND (prostate cancer); (urinary miRNA) AND (bladder cancer); (urinary miRNA) AND (renal cancer); (urinary miRNA) AND (testicular cancer); (urinary miRNA) AND (urothelial cancer). Of all, 1364 articles were screened. Only original studies in the English language on human specimens were considered for inclusion in our systematic review. Thus, a convenient sample of 60 original articles was identified. UmiRNAs are up- or downregulated in prostate cancer and may serve as potential non-invasive molecular biomarkers. Several umiRNAs have been identified as diagnostic biomarkers of urothelial carcinoma and bladder cancer (BC), allowing us to discriminate malignant from nonmalignant forms of hematuria. UmiRNAs could serve as therapeutic targets or recurrence markers of non-muscle-invasive BC and could predict the aggressivity and prognosis of muscle-invasive BC. In renal cell carcinoma, miRNAs have been identified as predictors of tumor detection, aggressiveness, and progression to metastasis. UmiRNAs could play an important role in the diagnosis, prognosis, and therapy of urological cancers.
Topics: Male; Humans; MicroRNAs; Testicular Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urologic Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Prostatic Neoplasms; Biomarkers, Tumor
PubMed: 37446024
DOI: 10.3390/ijms241310846 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692