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Nanoparticle-Mediated Small RNA Deliveries for Molecular Therapies
Published in D. Sakthi Kumar, Aswathy Ravindran Girija, Bionanotechnology in Cancer, 2023
Ramasamy Paulmurugan, Uday Kumar Sukumar, Tarik F. Massoud
Similar to siRNAs that are designed to target different cellular genes to achieve a certain functional effect, miRNAs are another group of small endogenous RNAs with similar structure and functional properties expressed in cells to regulate more than one cellular target (up to 80 genes) involved in multiple cellular pathways. MiRNAs have been used for therapeutic applications in treating various cellular diseases, including cancer. Carbon nanoparticles after different functionalizations have been used for the delivery of miRNA mimics and antisense miRNAs. We have recently shown that fluorescently labeled antisense-miRNA (Cy5-antisense-miRNA-21) can be delivered using reduced graphene oxide, to measure its functional hybridization with intracellular miRNA-21 by using optical imaging [30].
Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Published in Yashwant Pathak, Gene Delivery, 2022
Vineet Mahajan, Shruti Saptarshi, Yashwant Pathak
miRNAs are small non-coding RNAs that are involved in post-transcriptional gene silencing and regulation of gene expression via physiological and pathological mechanisms. miRNAs were first identified in the nematode, C.elegans, almost a decade ago.6 High-throughput sequencing technologies and computational analysis tools have been key to the discovery of miRNAs. miRNAs are small and single-stranded molecules, approximately 22 nucleotides in length (occurring as a hairpin like duplex) and exert their effect by binding to the 3′ untranslated region (3′UTR) of target messenger RNAs (mRNAs). This interaction is responsible for the degradation or translational inhibition of the target mRNA.
The Precision Medicine Approach in Oncology
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Patterns of miRNA expression are tightly controlled and have a significant impact on cell proliferation, apoptosis, and differentiation. Changes in the expression levels of miRNA can potentially promote tumorigenesis. Depending on the genes targeted, miRNAs can act as either tumor suppressors or oncogene activators. In many types of cancers, the tumor suppressor miRNAs are repressed while the oncogenic miRNAs are up-regulated. These changes can occur through chromosomal abnormalities or alterations to transcription factor binding. However, recent studies have shown that changes resulting from miRNA de-regulation can be reversed by treatment with chromatin-modifying drugs. Thus, miRNA is currently a promising target for novel epigenetic therapies.
MiR-3646 accelerates inflammatory response of Ang II-induced hVSMCs via CYP2J2/EETs axis in hypertension model
Published in Clinical and Experimental Hypertension, 2023
Runzhi Liu, Liying Zhong, Cong Wang, Yehai Sun, Wunjuan Ru, Wei Dai, Shengnan Yang, Aimin Zhong, XiuMei Xie, XiaoBin Chen, Shundong Li
MiRNAs are a class of non-coding RNAs that affect a variety of cellular biological activities and molecular targets (6). As post-regulators of gene expression, miRNAs regulate mRNA translation or degradation by directly binding to target genes, and 2–7 nucleotides of mature miRNAs are considered to recognize the most important region for complementary base pairing in the target gene (7). MiRNAs are involved in various diseases progression, especially in cardiovascular disease. For example, miR-217 serves as a biomarker of vascular aging and cardiovascular risk (8). Jiang et al. reported that miR-1 is closely related to endothelial inflammatory response and atherosclerosis (9). Mohammad Babaee et al. found that miRs-27a and FOXO1 genes are closely associated with inflammatory cytokines and have potential roles in atherosclerosis progression (10). MiR-3646 is a newly discovered miRNA involved in various disease progression. For example, miR-3646 promotes breast cancer progression by regulating tumor cell metastasis (11). Wang et al. showed that miR-3646 promotes lung adenocarcinoma progression by downregulating SORBS1 through JNK signaling pathway (12). Futhermore, miR-3646-RHOH axis accelerates coronary artery disease progression by regulating vascular inflammation and modulating the biological behavior of VSMCs (13). However, the role of miR-3646 in inflammatory response of VSMCs in hypertension model and its underlying molecular mechanism remain unclear.
Drug loaded implantable devices to treat cardiovascular disease
Published in Expert Opinion on Drug Delivery, 2023
Masoud Adhami, Niamh K. Martin, Ciara Maguire, Aaron J. Courtenay, Ryan F. Donnelly, Juan Domínguez-Robles, Eneko Larrañeta
miRNAs are a class of small single-stranded non-coding RNA molecules involved in the regulation of gene expression. Indeed, it has been shown that some miRNAs can be involved in the cardiovascular repair of the ischemic heart [128]. Despite the significant potential of this therapy, the delivery of these small molecules is still an essential factor for achieving a greater therapy success [129]. Thus, to improve the delivery and stability of these molecules different approaches have been evaluated. For instance, Li et al. developed a new miRNAs-containing 3D fibrin-based hydrogel platform containing miRNAs, which significantly enhanced the reprogramming of cardiac fibroblasts into functional CMs [130]. In a different work, Gabisonia et al. were able to deliver the human miRNA-199a by using an adeno-associated viral vector platform [131]. The outcomes of this study exhibited that infarcted pigs showed clear improvements in the contractile capacity of their hearts. Moreover, the muscle mass was increased, and scar size was reduced [131]. These results are in line with the de-differentiation and proliferation of CMs, thus suggesting the success of the used miRNAs therapy.
microRNAs Alterations of Myocardium and Brain Ischemia-Reperfusion Injury: Insight to Improve Infarction
Published in Immunological Investigations, 2022
Fatemeh Sabet Sarvestani, Negar Azarpira
miRNAs are short single chains of non-coding RNAs (length of 19–23 nucleotides). They are currently recognized as endogenous physiological regulators of gene expression by linking to the 3′UTR of target mRNAs. They were first identified in Caenorhabditis elegans in 1993 by Lee et al. (Lee et al. 1993). As yet, over 10000 miRNAs have been identified in different organisms through random cloning and sequencing (Krek et al. 2005). The biogenesis of miRNAs is a multi-stage process (Figure 1). It starts with the processing of RNA polymerase II/III transcripts post- or co-transcriptionally and produces pri- and pre-miRNA, respectively. After pre-miRNAs transition by exportin-5 to the cytoplasm, they are further processed by RNase III (Dicer) to become mature miRNAs (Devasthanam and Tomasi 2014; Wade et al. 2017). Subsequently, by loading onto the argonaute protein, the effector RNA-induced silencing complex is produced (Zhu et al. 2016). Many studies have shown that miRNAs regulated IRI in the heart and cerebrum after infarction and attenuated or promoted this condition by alteration of signaling cascade. In this review, we clarify several miRNAs that alter during IRI in these tissues and act by different pathways to change this status. Some miRNAs via common targets that related to IRI in these tissues are summarized in Tables 1 and 2.