miRNA: A Promising Therapeutic Target in Cancer

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(19), P. 11502 - 11502

Published: Sept. 29, 2022

microRNAs are small non-coding RNAs that regulate several genes post-transcriptionally by complementarity pairing. Since discovery, they have been reported to be involved in a variety of biological functions and pathologies including cancer. In cancer, can act as tumor suppressor or oncomiR depending on the cell type. Studies shown miRNA-based therapy, either inhibiting an inducing suppressor, is effective cancer treatment. This review focusses role miRNA therapeutic approaches with miRNAs how effectively delivered into system. We also summarized patents clinical trials progress for therapy.

Language: Английский

---

Trials and Tribulations of MicroRNA Therapeutics

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1469 - 1469

Published: Jan. 25, 2024

The discovery of the link between microRNAs (miRNAs) and a myriad human diseases, particularly various cancer types, has generated significant interest in exploring their potential as novel class drugs. This led to substantial investments interdisciplinary research fields such biology, chemistry, medical science for development miRNA-based therapies. Furthermore, recent global success SARS-CoV-2 mRNA vaccines against COVID-19 pandemic further revitalized RNA-based immunotherapies, including approaches treatment. Consequently, RNA therapeutics have emerged highly adaptable modular options therapy. Moreover, advancements chemistry delivery methods been pivotal shaping landscape immunotherapy, approaches. biotechnology pharmaceutical industry witnessed resurgence incorporating immunotherapies miRNA into programs. Despite progress preclinical research, field remains its early stages, with only few progressing clinical development, none reaching phase III trials or being approved by US Food Drug Administration (FDA), several facing termination due toxicity issues. These setbacks highlight existing challenges that must be addressed broad application therapeutics. Key include establishing sensitivity, specificity, selectivity towards intended targets, mitigating immunogenic reactions off-target effects, developing enhanced targeted delivery, determining optimal dosing therapeutic efficacy while minimizing side effects. Additionally, limited understanding precise functions miRNAs limits utilization. viable treatment, they technically economically feasible widespread adoption As result, thorough risk evaluation is crucial minimize prevent overdosing, address other Nevertheless, diseases evident, future investigations are essential determine applicability settings.

Language: Английский

---

The potential use of mesenchymal stem cells-derived exosomes as microRNAs delivery systems in different diseases

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Jan. 23, 2023

Abstract MicroRNAs (miRNAs) are a group of small non-coding RNAs that regulate gene expression by targeting mRNA. Moreover, it has been shown miRNAs changed in various diseases, such as cancers, autoimmune disease, infectious and neurodegenerative Diseases. The suppression miRNA function can be easily attained utilizing anti-miRNAs. In contrast, an enhancement achieved through the utilization modified mimetics. discovery appropriate carriers body become interesting subject for investigators. Exosomes (EXOs) therapeutic efficiency safety transferring different cellular biological components to recipient cell have attracted significant attention their capability carriers. Mesenchymal stem cells (MSCs) recognized generate wide range EXOs (MSC-EXOs), showing MSCs may effective EXO generation clinically measure compared other origins. MSC-EXOs widely investigated because immune attributes, tumor-homing flexible characteristics. this article, we summarized features MSC-EXOs, including production, purification, loading methods modification targeted delivery diseases. Graphical abstract

Language: Английский

---

SGLT2 inhibitor empagliflozin downregulates miRNA-34a-5p and targets GREM2 to inactivate hepatic stellate cells and ameliorate non-alcoholic fatty liver disease-associated fibrosis

Metabolism, Journal Year: 2023, Volume and Issue: 146, P. 155657 - 155657

Published: July 6, 2023

Language: Английский

---

The miRNA–target interactions: An underestimated intricacy

Nucleic Acids Research, Journal Year: 2023, Volume and Issue: 52(4), P. 1544 - 1557

Published: Nov. 30, 2023

Abstract MicroRNAs (miRNAs) play indispensable roles in posttranscriptional gene regulation. Their cellular regulatory impact is determined not solely by their sheer number, which likely amounts to >2000 individual miRNAs human, than the effectiveness of single miRNAs. Although, one begins develop an understanding complex mechanisms underlying miRNA–target interactions (MTIs), overall knowledge MTI functionality still rather patchy. In this critical review, we summarize key features mammalian MTIs. We especially highlight latest insights on (i) dynamic make-up miRNA binding sites including non-canonical sites, (ii) cooperativity between (iii) adaptivity MTIs through sequence modifications, (iv) bearing intra-cellular localization changes and (v) role cell type status specific interaction partners. The biology discussed against background state-of-the-art approaches with particular emphasis experimental strategies for evaluating functionality.

Language: Английский

---

MicroRNAs; their therapeutic and biomarker properties

Cellular Molecular and Biomedical Reports, Journal Year: 2023, Volume and Issue: 3(2), P. 73 - 88

Published: April 11, 2023

MicroRNAs (miRNAs) are, small (roughly 19–25 nucleotides in length), conserved, non-coding, single-stranded, and functional RNA molecules with the properties of gene expression regulation through mRNA degradation, translation repression, deadenylation as well silencing via histone methylation. They even have ability to increase levels. The biogenesis miRNAs is divided into two canonical non-canonical pathways. second pathway has a divergent mechanism for miRNAs. can be transcribed from specific genes or introns protein-coding genes. A single miRNA species control hundreds genes, also one target different These been identified eukaryotic organisms such mammals plants viruses. play an inevitable role life cycle cells. are involved any biological processes cell proliferation differentiation, apoptosis, signaling, defense responses their spatio-temporal manner. Aberrant large number disorders, which illustrates great potential applied diagnosis treatment various diseases. inhibitors (anti-miRs) artificial (miRNA mimics) general approaches balance dysregulated levels that make it possible treat disorders. In this study, general, miRNAs, origin viral detection procedures, silico analysis tools, miRNA-based therapies obstacles, non-invasive biomarkers discussed. Finally, stated importance dietary

Language: Английский

---

miRNAs: The Road from Bench to Bedside

Genes, Journal Year: 2023, Volume and Issue: 14(2), P. 314 - 314

Published: Jan. 25, 2023

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

Language: Английский

---

Human umbilical cord mesenchymal stem cells derived exosome shuttling mir-129-5p attenuates inflammatory bowel disease by inhibiting ferroptosis

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: June 12, 2023

Abstract Background Ferroptosis, a unique form of non-apoptotic cell death, is dependent on iron and lipoperoxidation, has been shown to be associated with the pathogenesis inflammatory bowel disease (IBD). Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) are involved in survival, immune conditioning, damage repair. However, relationship between hucMSC-Ex, IBD, ferroptosis unknown. This paper explores role hucMSC-Ex repair IBD through regulation signaling pathway. Results In this study, we used small RNA sequencing find that miR-129-5p was highly expressed by predicting its targeting ACSL4, verified effect mice vitro human colonic epithelial cells (HCoEpiC) vivo. We found reduces intestinal ACSL4 which provides new strategies for prevention treatment IBD. Conclusion conclusion, our results demonstrate relieves inhibit lipid peroxidation (LPO) ferroptosis, reducing inflammation repairing damages. Graphic abstract Mechanism inhibiting cells. System Xc − mediates transport extracellular cystine into cell, gets reduced cysteine participate GSH-mediated metabolism. GPX4 strongly inhibits helping scavenge reactive oxygen species. The depletion GSH correlates decreased GPX4, imbalance antioxidant system leads formation toxic phospholipid hydroperoxide, promotes occurrence participation irons. HucMSC-Ex ability relieve intracellular system. Ferric ions enter cytosol DMT1 peroxidation. can reduce expression alleviate process. HucMSC-Ex-derived targets an enzyme conversion PUFAs phospholipids cells, positive regulator Abbreviations: GSH, glutathione; glutathione peroxidase 4; GSSG, oxidized DMT1, divalent metal transporter 1; acyl-CoA synthetase long-chain family member PUFAs, polyunsaturated fatty acids; ALOXs, lipoxygenases; CoA, coenzyme A; PL, phospholipid; PLOOH, hydroperoxides, LOH, alcohols; LPO,

Language: Английский

---

Gender Differences in the Pathogenesis and Risk Factors of Hepatocellular Carcinoma

Biology, Journal Year: 2023, Volume and Issue: 12(7), P. 984 - 984

Published: July 11, 2023

Several chronic liver diseases are characterized by a clear gender disparity. Among them, hepatocellular carcinoma (HCC) shows significantly higher incidence rates in men than women. The different epidemiological distribution of risk factors for disease and HCC only partially accounts these differences. In fact, the is an organ with recognized sexual dysmorphism extremely sensitive to action androgens estrogens. Sex hormones act modulating developing influencing its aggressiveness, response treatments, prognosis. Furthermore, estrogens able modulate other cofactors damage (e.g., HBV infection, obesity), their carcinogenic power. purpose this review examine related as well pathophysiological mechanisms involved, particular reference central role played sex hormones.

Language: Английский

---

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 8, 2023

Lung cancer (LC) is a heterogeneous disease with high malignant degree, rapid growth, and early metastasis. The clinical outcomes of LC patients are generally poor due to the insufficient elucidation pathological mechanisms, low efficiency detection assessment methods, lack individualized therapeutic strategies. Non-coding RNAs (ncRNAs), including microRNA (miRNA), long non-coding RNA (lncRNA), circular (circRNA), endogenous regulators that widely involved in modulation almost all aspects life activities, from organogenesis aging immunity cancer. They commonly play vital roles various biological processes by regulating gene expression via their interactions DNA, RNA, or protein. An increasing amount studies have demonstrated ncRNAs closely correlated initiation development LC. Their dysregulation promotes progression distinct such as influencing protein activity, activating oncogenic signaling pathways, altering specific expression. Furthermore, some present certain values biomarker candidates targets for patients. A complete understanding mechanisms may be highly beneficial developing ncRNA-based therapeutics This review mainly focuses on intricate miRNA, lncRNA, circRNA discuss underlying applications treatment.

Language: Английский

---