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MicroRNAs (miRNAs or miRs) are a family of small non‑coding RNAs that regulate gene expression by the sequence-selective targeting of mRNAs, leading to translational repression or mRNA degradation, depending on the degree of complementarity with target mRNA sequences. miRNAs play a crucial role in cancer. In the case of breast tumors, several studi...
Context in source publication
Context 1
... nucleic acid (PNA) (Fig. 4) is a DNA analogue in which the sugar-phosphate backbone is replaced by N-(2-aminoethyl) glycine units (79-84). These molecules efficiently hybridize with complementary DNA and RNA, forming a double helix with Watson-Crick base pairs (79,80). Accordingly, PNA has been suggested for use in antisense and anti-gene therapy in a number of ...
Citations
... [7] Noncoding RNAs (ncRNAs) are nonprotein-coding RNAs that play important roles in regulating the expression of target genes in numerous biological processes that facilitate the occurrence and development of various diseases. [8,9] NcRNAs are distinguished as long noncoding RNAs (lncRNAs) and small ncRNAs (sncRNAs) according to nucleotide length. [10] LncRNAs are longer than 200 nucleotides, and sncRNAs are smaller than 200nucleotides. ...
Background
In recent years, many studies have focused on the relationship between noncoding RNAs (ncRNAs) and Kawasaki disease (KD). Studies have indicated that ncRNAs are associated with the occurrence and development of KD. Thus, we performed a systematic review and meta-analysis to investigate the diagnostic value of ncRNAs in KD patients.
Methods
We searched the PubMed, Web of Science, Embase and Cochrane Library, China National Knowledge Infrastructure, VIP, China Biology Medicine disc databases, and Wanfang databases until August 25, 2023 and screened all eligible studies focusing on the diagnostic performance of ncRNAs in KD patients.
Results
In total, 535 articles were found, and 28 articles were included in this systematic review and meta-analysis. The calculated area under the curve value was 0.880 (95% confidence intervals, 0.840–0.900). The pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio were 0.790, 0.830, 4.610, and 0.260, respectively. The pooled diagnostic odds ratio was 17.890 (95% confidence intervals, 13.110–24.420), indicating a relatively good diagnostic performance of the ncRNAs for detecting KD. In addition, the diagnostic value of micro RNAs in KD was better than that of long noncoding RNAs and circular noncoding RNAs. A subgroup analysis by specimen indicated a better diagnostic value of ncRNAs in plasma and platelet than serum. The diagnostic accuracy of ncRNAs was better in febrile controls than in healthy control groups, indicating a relatively good accuracy in distinguishing KD patients from febrile diseases.
Conclusions
This systematic review and meta-analysis demonstrated that ncRNAs could be used as novel biomarkers for detecting KD. More studies should be conducted in the future to verify the diagnostic values of ncRNAs in KD.
... It has been proven that miRNA functions as an oncogene or tumor suppressor gene in carcinogenesis. It binds to complementary mRNA and thereby inhibits mRNA translation and inactivates target genes [33]. ...
Uveal melanoma (UM) is an ocular tumor with a dismal prognosis. It is the most frequent primary intraocular tumor in adults. The primary goal of treatment for uveal melanomas is to prevent metastasis. Despite outstanding advances in the diagnosis and treatment of primary UM, nearly 50% of patients develop metastases via hematogenous dissemination. Estimation of prognosis for patients with UM can be achieved by detecting genetic alterations or epigenetic changes in the tumor tissues. However, these techniques are not always available. The clinicopathological characteristics with limited accuracy are widely used instead to predict metastatic potential. Identifying novel markers with prognostic potential can help refine the prognosis of UM patients. As we know, no existing therapy has a significantly better impact on preventing metastasis. Based on published theories, the key role is existing micrometastasis before therapy starts. Researchers are focusing on developing adjuvant systemic therapy for metastatic UM. Getting to know the cause of metastatic uveal melanoma is crucial in it.
... Generally, miRNAs involved in cancer are either tumor suppressors or oncogenes, depending on the expression levels [107]. Overexpressed miRNAs, oncogenes, with a crucial role in the initiation and progression of cancer, have been termed oncomiRs [108]. As of February 2022, more than 40,000 free-full peer-reviewed articles dedicated to the investigation of the role of miRNA in cancer by diverse experimental approaches are available in the PubMed depository (https://pubmed.ncbi.nlm.nih.gov/?term=mirna+cancer&filter=simsearch2.ffrft ...
Canine mammary cancer (CMC), similar to human breast cancer (HBC) in many aspects, is the most common neoplasm associated with significant mortality in female dogs. Due to the limited therapy options, biomarkers are highly desirable for early clinical diagnosis or cancer progression monitoring. Since the discovery of microRNAs (miRNAs or miRs) as post-transcriptional gene regulators, they have become attractive biomarkers in oncological research. Except for intracellular miRNAs and cell-free miRNAs, exosome-derived miRNAs (exomiRs) have drawn much attention in recent years as biomarkers for cancer detection. Analysis of exosomes represents a non-invasive, pain-free, time- and money-saving alternative to conventional tissue biopsy. The purpose of this review is to provide a summary of miRNAs that come from non-exosomal sources (canine mammary tumor, mammary tumor cell lines or canine blood serum) and from exosomes as promising biomarkers of CMC based on the current literature. As is discussed, some of the miRNAs postulated as diagnostic or prognostic biomarkers in CMC were also altered in HBC (such as miR-21, miR-29b, miR-141, miR-429, miR-200c, miR-497, miR-210, miR-96, miR-18a, miR19b, miR-20b, miR-93, miR-101, miR-105a, miR-130a, miR-200c, miR-340, miR-486), which may be considered as potential disease-specific biomarkers in both CMC and HBC.
... microRNAs (miRNAs) are small, single-stranded RNA regulating gene expression [11]. They regulate substantial physiological and pathological processes including cell proliferation, cell differentiation, and cell death. ...
Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR-195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma.
... MiRNA post-transcriptional regulation of mRNA is essential in processes such as cell cycle control, cell proliferation, apoptosis, differentiation, migration, metabolism and stem cell maintenance in both normal and cancerous cells (Jansson and Lund 2012;Rothschild 2014;Fish et al. 2020). The involvement of miRNAs in oncogenesis and cancer progression has made them very attractive targets in oncology research since their discovery almost three decades ago (Ambros 1989;Piva et al. 2013;Zadran et al. 2013;Schultz et al. 2014;Tang et al. 2016); the activity of a few miRNAs has been modulated for therapeutic applications (Rothschild 2014;Zhang et al. 2015). MiRNA expression has been reported to be involved in resistance to chemotherapy in cancer cells. ...
Canine mammary gland tumour (CMT) commonly affects the female dog. The objective of this study was to develop a doxorubicin-resistant CMT cell line and determine its in vitro and in vivo characteristics, including mRNA and microRNA (miRNA) expression profiles. Doxorubicin-resistant CMT-Star cells were developed from CMT-Stylo cells. The cells were characterized, including tumorigenicity in NOD/SCID mouse models. MiRNA and mRNA expression of the two cell lines were profiled and clustered. ATP binding cassette subfamily B member 1 (ABCB1) and subfamily G member 2 (ABCG2) expressions were significantly increased in the CMT-Star cell line. CMT-Star cells also had altered expression of 785 genes and 14 miRNAs. Downregulating plasminogen (PLG) and plasminogen activator urokinase (PLAU) while upregulating transforming growth factor beta receptor 3 (TGFBR3), epidermal growth factor receptor 1 (EGFR1) and ABCB1 rendered CMT-Star cells less proliferative, less invasive and more resistant to chemotherapeutic drugs. The upregulated miRNAs in CMT-Star cells include miRNA-191, -29a, -107, -99b, -874, -93 and -210, while the downregulated miRNAs include miRNAs-106a, -92a, -92b, -155 and -15b. TGFβR, EGF receptor 1 and Wnt signalling are enriched in doxorubicin-resistant CMT-Star cells and could be potential therapeutic targets in dogs with doxorubicin-resistant CMT.
... Breast cancer mostly begins in the areas of the breast tissue which are composed of lobules (ductal cancer), i.e. milk-producing organs that connect to the nipple, and then spread to the whole body. 9 For females, the lack of physical activity, alcohol, obesity, ionizing radiation, consumption, genetic disorder, pollution, aging, diet, vitamin D deficiency, inorganic and organic chemicals, family history, initial menstruation at a young age, lack of exposure to sunlight, delayed child-bearing, and adaptation of Western way of life are all risk factors for the progression and proliferation of breast cancer. 10 Environmental factors affect over 93% of new cancer victims, while the genetic factors influenced only 7%. ...
... After that, again deviation starts at 45-49 ns and from 51 ns, the system attains stability and shows stable trajectory from then on. At different intervals of time, different fluctuations can be seen, i.e. around 5,9,14,26,30,44, and 49 ns, which show reasonable flexibility and stability of the complex L17-ER. The complex L57-ER shows an average deviation of $ 3 Å at 24 ns. ...
Breast cancer is the most common cancer among women worldwide. Breast cancer is caused by the overexpression of genes that facilitate breast cell proliferation. Estrogen receptor alpha (ER[Formula: see text]) mediation is mostly responsible for the development of malignant tumors by regulating the transcription of various genes as a transcription factor. ER[Formula: see text] is regarded as an important receptor for the proliferation of this disease and its inhibition is necessary for the treatment of breast cancer. In our study, the aim is to find out potential inhibitors for ER[Formula: see text] by docking 100 anticancer constituents of different halogen-based derivatives against ER[Formula: see text]. Among the 100 [Formula: see text]-based derivatives, 20 ligands were selected based on the interaction energy ranging from [Formula: see text]6.7[Formula: see text]kcal/mol to [Formula: see text]8.2[Formula: see text]kcal/mol and lower values of inhibition constant (0.92–11.77[Formula: see text][Formula: see text]). We have performed a comprehensive analysis of five most popular ligands (L17, L57, L61, L67, and L70) among these 20 selected derivatives. The interaction analysis is mainly stabilized by making different interactions including hydrogen bonding, hydrophobic, electrostatic, and halogen bonding with the active site of ER[Formula: see text]. A quantum study based on frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), and global chemical reactivity descriptor (GCRD) is carried out to explore the structural chemistry of our most popular ligands which indicates that they are quite reactive and kinetically stable. Additionally, we also assess the ADMET profiles to predict the toxicity and drug-likeness of our lead compounds. Our selected ligands have the highest absorption and good clearance rate and have no AMES toxicity, skin sensitization, and hepatotoxicity. Molecular dynamics simulations were run to check the conformational stability of apo form of ER[Formula: see text] and complex state, at 60-ns time scale. The molecular dynamics simulations are based on the plots of RMSD, RMSF, [Formula: see text], SASA, and the number of H-bonds. The results of RMSD and RMSF showed that the lead compounds L17, L57, L61, L67, and L70 are most stable and have no significant residual fluctuations and deviation. The analysis of the plots of [Formula: see text], SASA, and the number of H-bonds revealed that the complexes L17, L57, and L70 are most stable. So, the lead anticancer compounds L17, L57, L61, L67, and L70 are the most promising inhibitors against ER[Formula: see text] of breast cancer. The comprehensive analysis of all studied parameters highlighted that our selected ligands have great potential to inhibit ER[Formula: see text]. So, it can be concluded that the selected halogen-based derivatives can promote rational drug design for the target therapies of ER[Formula: see text] of breast cancer.
... miRNAbased therapeutic oligonucleotides can be developed as miRNA mimics or anti-miRNAs (ASOs). miRNA mimics imitate miRNA functions, while anti-miRNAs bind to miRNAs complementarily and deactivate their functions through RNase H-mediated degradation or the steric blockage mechanism [107,108]. Like the chemically modified ASOs targeting mRNAs/pre-mRNAs, anti-miRNAs are usually composed of nucleotide analogues instead of unmodified nucleotides to obtain improved nuclease stability and target miRNAbinding affinity. For example, miRNA-92a is a potential therapeutic target of cardiovascular diseases with CKD as it mediates endothelial dysfunction in CKD [109]. ...
... miRNA-based therapeutic oligonucleotides can be developed as miRNA mimics or anti-miRNAs (ASOs). miRNA mimics imitate miRNA functions, while anti-miRNAs bind to miRNAs complementarily and deactivate their functions through RNase H-mediated degradation or the steric blockage mechanism [107,108]. Like the chemically modified ASOs targeting mRNAs/pre-mRNAs, anti-miRNAs are usually composed of nucleotide analogues instead of unmodified nucleotides to obtain improved nuclease stability and target miRNA-binding affinity. For example, miRNA-92a is a potential therapeutic target of cardiovascular diseases with CKD as it mediates endothelial dysfunction in CKD [109]. ...
Chronic kidney disease (CKD) is a global public health issue that places an increasing burden on the healthcare systems of both the developed and developing countries. CKD is a progressive and irreversible condition, affecting approximately 10% of the population worldwide. Patients that have progressed to end-stage renal disease (ESRD) require expensive renal replacement therapy, i.e., dialysis or kidney transplantation. Current CKD therapy largely relies on the use of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs). However, these treatments by no means halt the progression of CKD to ESRD. Therefore, the development of new therapies is urgently needed. Antisense oligonucleotide (ASO) has recently attracted considerable interest as a drug development platform. Thus far, eight ASO-based drugs have been granted approval by the US Food and Drug Administration for the treatment of various diseases. Herein, we review the ASOs developed for the identification of CKD-relevant genes and/or the simultaneous development of the ASOs as potential therapeutics towards treating CKD.
... Recent evidence in multiple cancers (9)(10)(11)(12)(13) including breast cancer (14)(15)(16) identify microRNAs (miRNAs) as novel gene expression regulators and potential biomarkers (17)(18)(19). miRNAs are small non-coding RNAs approximately 19 to 25 nucleotides in length; they control gene expression by targeting selective-sequences of mRNAs, inducing translational repression or complete mRNA degradation (20). miRNA expression profiles have the ability to identify molecular breast cancer subtypes (21,22) and can differentiate between basal and luminal subtypes (23). ...
Background
Increased expression of the progesterone receptor membrane component 1, a heme and progesterone binding protein, is frequently found in triple negative breast cancer tissue. The basis for the expression of PGRMC1 and its regulation on cellular signaling mechanisms remain largely unknown. Therefore, we aim to study microRNAs that target selective genes and mechanisms that are regulated by PGRMC1 in TNBCs.
Methods
To identify altered miRNAs, whole human miRNome profiling was performed following AG-205 treatment and PGRMC1 silencing. Network analysis identified miRNA target genes while KEGG, REACTOME and Gene ontology were used to explore altered signaling pathways, biological processes, and molecular functions.
Results
KEGG term pathway analysis revealed that upregulated miRNAs target specific genes that are involved in signaling pathways that play a major role in carcinogenesis. While multiple downregulated miRNAs are known oncogenes and have been previously demonstrated to be overexpressed in a variety of cancers. Overlapping miRNA target genes associated with KEGG term pathways were identified and overexpression/amplification of these genes was observed in invasive breast carcinoma tissue from TCGA. Further, the top two genes ( CCND1 and YWHAZ ) which are highly genetically altered are also associated with poorer overall survival.
Conclusions
Thus, our data demonstrates that therapeutic targeting of PGRMC1 in aggressive breast cancers leads to the activation of miRNAs that target overexpressed genes and deactivation of miRNAs that have oncogenic potential.
... Non-coding RNAs (ncRNAs) are functional RNAs which are not coded for protein production but serve important regulatory role in numerous biological processes [7]. According to the nucleotides length threshold of 200 nucleotides, ncRNAs are classified into small ncRNAs (sncRNAs) and long ncRNAs (lncRNAs) [8,9]. ...
Background
Genetic, environmental and epigenetical factors may play important roles in the pathogenesis of polycystic ovary syndrome (PCOS), however the etiology of PCOS remains unclear. Studies indicated that non-coding RNAs (ncRNAs) were involved in the occurrence and development of PCOS. Thus, we aim to perform a systematic review and meta-analysis to investigate the presence and dysregulated expression of ncRNAs in human PCOS.
Methods
We searched in PubMed, Medline, Web of Science and Embase until July 2019 and summarized all eligible publications focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and small interfering RNAs (siRNAs) in PCOS.
Results
Sixty-seven articles were included in our systematic review and 9 articles were included in meta-analysis. There is little overlap between studies when comparing miRNA profiles. Sensitivity analysis showed that the expression of miR-93 was upregulated in PCOS patients (WMD 0.75, P < 0.00001), without heterogeneity among remaining studies (I ² = 0%).
Conclusion
A large number of ncRNAs with altered levels were observed in plasma, serum, follicular fluid, granulosa cells or other issues from PCOS patients. Aberrant ncRNAs expression in PCOS may lead to aberrant steroidogenesis, adipocyte dysfunction, altered ovarian cell proliferation and/or apoptosis and have the potential to be used as diagnostic biomarkers.
... MiRNA level variations were analyzed comparing normal vs. neoplastic tissues [17,18] in several BC subtypes [19] with different responses to endocrine therapy [20]. Several miRNAs were related to pathogenesis of TNBC [21,22] and might represent potential predictors of anticancer drugs efficacy and prognosis [23][24][25]. Recognizing gene expression regulator-classified miRNAs as epigenetic elements involved in cancer development means that they might be potentially used as therapeutic targets and diagnostic/prognostic biomarkers in order to achieve high accuracy in tumor classification [26]. ...
Simple Summary
Triple Negative breast cancer (TNBC) is an aggressive tumor showing high histological grade, high recurrence, and frequent metastasis, accounting for about 25% of breast cancer-related deaths. Emerging roles and molecular mechanisms by which miRNAs impact pathogenesis and prognosis of basal-phenotype TNBC and their potential clinical utility are analyzed in the present review. Progress achieved in TNBC molecular taxonomy had minimal clinical impact, while miRNAs could act as prognostic/predictive biomarkers for TNBC subtypes. As there are currently no other therapeutic options to treat TNBC apart from chemotherapy, various studies were reviewed to draw the conclusion that ncRNAs might be candidates for drug development and drug resistance. Targeted approaches to epigenetic mechanisms and clarification of the molecular mechanisms of specific miRNAs in TNBC subtypes are fully justified. This review might provide a collection of biomarkers potentially useful in clinical settings and shows that the combination of miRNA-based therapeutic strategies with conventional therapies might synergize anticancer effects improving patient outcome.
Abstract
Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.
