MicroRNA - Volume 11, Issue 3, 2022

MicroRNAs constitute small non-coding RNAs that play a pivotal role in regulating the translation and degradation of mRNA and have been associated with many diseases. Artificial Intelligence (AI) is an evolving cluster of interrelated fields, with machine learning (ML) standing out as one of the most prominent AI fields, with a plethora of applications in almost every aspect of human life. ML could be defined as computer algorithms that learn from past data to predict future data. This review comprehensively reviews the current applications of microRNA-based ML models in healthcare. The majority of the identified studies investigated the role of microRNA-based ML models in the management of cancer and specifically gastric cancer (maximum diagnostic accuracy (Accmax): 94%), pancreatic cancer (Accmax: 93%), colorectal cancer (Accmax: 100%), breast cancer (Accmax: 97%), ovarian cancer, neck squamous cell carcinoma, liver cancer, lung cancer (Accmax: 100%), and melanoma. Except for cancer, microRNA-based ML models have been applied for a plethora of other diseases, including ulcerative colitis (Accmax: 92.8%), endometriosis, gestational diabetes mellitus (Accmax: 86%), hearing loss, ischemic stroke, coronary heart disease (Accmax: 96%), tuberculosis, pulmonary arterial hypertension (Accmax: 83%), dementia (Accmax: 82.9%), major cardiovascular events in end-stage renal disease patients, and alcohol dependence (Accmax: 79.1%). Our findings suggest that the development of microRNA-based ML models could be used to enhance the diagnostic accuracy of a plethora of diseases while at the same time substituting or minimizing the use of more invasive diagnostic means (such as endoscopy). Even not as fast as anticipated, AI will eventually infiltrate the entire healthcare industry. AI is the key to a clinical practice where medicine's inherent complexity is embraced. Therefore, AI will become a reality that physicians should conform with to avoid becoming obsolete.

Viruses are microscopic biological entities that can cause diseases. Viruses require a host cell to replicate and generate progeny. Once inside, viruses hijack the main cellular machinery for their benefit, disrupting cell functions and causing detrimental effects on cell physiology. MicroRNAs are short, non-coding RNAs that regulate gene expression. Recent works have shown that cell-miRNAs can modulate antiviral defense during viral infection, and viruses can disrupt these existing miRNA networks. Furthermore, multiple RNA viruses encode their own miRNAs to evade the host immune response. In this review, we analyze the activities of both, miRNAs as pro-viral modulators and miRNAs as anti-viral agents and their relationship with the development of the disease.

Background: MicroRNAs (miRNAs) are small noncoding RNA molecules involved in the post-transcriptional regulation of genes. Deregulated expression of miRNAs is involved in different pathogenic mechanisms, particularly colorectal cancer (CRC) carcinogenesis. Due to their stability and accessibility, circulating miRNAs represent a new family of biomarkers with great potential. Therefore, certain miRNAs can be used as diagnostic biomarkers in CRC. Objective: This systematic analysis aimed to explore the individual efficacy of the most investigated blood-based miRNAs for CRC diagnosis, namely miR-21, miR-29a and miR-92a. Methods: Articles were retrieved from databases such as PubMed and Google Scholar, and studies designed to evaluate the diagnostic value of microRNAs in CRC were then selected. We subsequently explored the diagnostic accuracy of each miRNA using parameters such as (SE, SPE, PLR, NLR). The meta-analysis was performed using the Review Manager (Revman) 5.4 software and the Meta Disc software. Results: Our results suggested that serum miR-21 levels showed great potential as a diagnostic molecular marker. The overall pooled results for sensitivity, specificity, area under the curve (AUC), PLR, and NLR were 78%, 91%, 0.9519, 8.12 and 0.17, respectively. Conclusion: miRNAs have become increasingly important in the diagnosis of CRC. Based on these findings, circulating miR-21 levels may have a potential value for early detection and might be used as a novel diagnostic biomarker for CRC.

Background: The transforming growth factor-beta1 (TGF-β1)-induced epithelial-tomesenchymal transition (EMT) has a crucial effect on the progression and metastasis of lung cancer cells. Objective: The purpose of this study was to investigate whether microRNA (miR)-16 can suppress TGF-β1-induced EMT and proliferation in human lung adenocarcinoma cell line (A549). Methods: Quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-16. The hallmarks of EMT were assessed by RT-qPCR, Western blotting, and cell proliferation assay. A bioinformatics tool was used to identify the putative target of miR-16. The activation of TGF-β1/Smad3 signaling was analysed using Western blotting. Results: Our results showed that miR-16 expression was significantly down-regulated by TGF-β1 in A549 cells. Moreover, agomir of miR-16 suppressed TGF-β1-induced EMT and cell proliferation. Computational algorithms predicted that the 3’-untranslated regions (3’-UTRs) of Smad3 are direct targets of miR-16. In addition, miR-16 mimic was found to inhibit the TGF-β1-induced activation of the TGF-β1/Smad3 pathway, suggesting that miR-16 may function partly through regulating Smad3. Conclusion: Our results demonstrated that overexpression of miR-16 suppressed the expression and activation of Smad3, and ultimately inhibited TGF-β1-induced EMT and proliferation in A549 cells. The present findings support further investigation of the anti-cancer effect of miR-16 in animal models of lung cancer to validate the therapeutic potential.

Background: The fetus grows in a sterile womb environment. After birth, the newborn immune system has two immediate hurdles to clear. First immediate suppression of the womb compatible immune system and turn on the immune system of the newborn that can counter the antigenic world. The underlying mechanism of immune fluctuation by milk microRNAs (miRNAs) can be crucial for the treatment of critical or premature newborn. Methods: We collected fourteen samples of each colostrum and mature milk from lactating mothers, four samples of each were used for microarray analysis, and the other ten were used for miRNA expression profiling by real-time PCR. Results: From the microarray, 154 differentially expressed miRNAs were identified, whereas 49 miRNAs were revealed as immune-related miRNAs based on a literature study. Among the 49 miRNAs, 33 were already shown as strongly validated immune-related miRNAs (validated by qPCR, Western Blot, and Luciferase assay) and were considered for further analysis. Twenty-two miRNA expressions were analysed by real-time PCR as their Ct values were within considerable limits. Twelve numbers of miRNAs were significantly downregulated in mature milk compared to colostrum, which were again subjected to bioinformatics analysis to predict the biological mechanisms behind the differentially expressed miRNAs. Conclusion: This study shed light on the human milk exosome miRNA expression dynamics during lactation and their possible role in the gradual skewing of the newborns' immune system. The information is crucial for the development and onset of sepsis in premature newborns in the NICU.

Background: Hematologic malignancies are among fatal diseases with different subtypes. Acute myeloid leukemia (AML) is a subtype showing a high invasion rate to different tissues. Objective: AML patients, even after treatment, show an increased rate of recurrence, and this relapsed profile of AML has turned this malignancy into big challenges in the medical scope. Methods: In the current study, we aimed to investigate hub-genes and potential signaling pathways in AML recurrence. Two expression profiles of genes and non-coding RNAs were extracted from the Gene Expression Omnibus (GEO) database. Target genes of identified miRNAs were predicted through bioinformatics tools. GO and KEGG pathway enrichment analyses were conducted to discover common target genes and differentially expressed genes. Protein128;protein interaction (PPI) network was constructed and visualized through the STRING online database and Cytoscape software, respectively. Hub-genes of constructed PPI were found through the CytoHubba plugin of Cytoscape software. Results: As a result, 109 differentially expressed genes and 45 differentially expressed miRNAs were found, and the top enriched pathways were immune response, xhemokine activity, immune System, and plasma membrane. The hub-genes were TNF, IL6, TLR4, VEGFA, PTPRC, TLR7, TLR1, CD44, CASP1, and CD68. Conclusion: The present investigation based on the in silico analysis and microarray GEO databases may provide a novel understanding of the mechanisms related to AML relapse.

Background: In 2019, severe acute respiratory coronavirus II (or SARS-COV-2) emerged in Wuhan, China, rapidly becoming a global pandemic. Coronavirus genus (Coronaviridae) has the largest single-stranded positive-sense RNA genome (~30 kb) among the human infected single-stranded RNA viruses. Objectives: For the study of active therapeutic plant-derived miRNA(s), it may be possible to uptake the miRNAs and their biological role in the host cell. In this study, we bioinformatically searched plant miRNAs that can potentially interact with the Sars-CoV-2 genome within the 3’- UTR region and have prompt antiviral activity. Materials and Methods: We searched the plant miRNAs that target the 3’-UTR flanking region of the Sars-CoV-2 genome by employing the RNAHybrid, RNA22, and STarMir miRNA/target prediction tools. Results: The RNAHybrid algorithm found 63 plant miRNAs having hybridization energy with less or equal to -25 kcal.mol-1. Besides, RNA22 and STarMir tools identified eight interactions between the plant miRNAs and the targeted RNA sequence. pvu-miR159a. 2 and sbi-miR5387b were predicted as the most effectively interacting miRNAs in targeting the 3’-UTR sequence, not only by the RNA22 tool but also by the STarMir tool at the same position. However, the GC content of the pvumiR159a. 2 is 55% instead of sbi-miR5387b, which is a GC enriched sequence (71.43%) that may activate TLR receptors. Conclusion: In our opinion, they are potent plant-derived miRNA candidates that have a great chance of targeting the Sars-CoV-2 genome in the 3’-UTR region in vitro. Therefore, we propose pvu-miR159a.2 for studying antiviral miRNA-based therapies without any essential side effects in vivo.

Background: Breast cancer (BC) is one of the main causes of cancer-related death in women worldwide. It is necessary to find methods for prognosis and early detection of BC. MicroRNAs inhibit the expression of special target genes at the post-transcriptional stage and have a fundamental role in various cancers. They function as oncogenes or tumor suppressors. MiR-125a- 5p acts as a tumor suppressor in some cancers through a signal transducer and activator of transcription 3 (STAT3) suppression. STAT3 is activated in response to cytokines and growth factors, affecting the transcription of target genes. Objective: We examined the association between miR-125a-5p and STAT3 expression levels in breast cancer patients for the first time through a case-control study on an Iranian population. Methods: Total RNAs were extracted from breast cancer and healthy tissues using TRIzol Reagent. Complementary DNA synthesis was performed, and Real-time PCR was done using miR-125a and STAT3-specific primers. GAPDH and U48 genes were used as internal controls. Statistical analysis of the results was conducted by SPSS v.19.0 software. Results: We obtained a significant association between miR-125a-5p down-regulation and breast cancer disease (0.4333 in patients vs. 1.656 in controls, p-value = 0.009). STAT3 expression was significantly up-regulated in BC samples relative to healthy subjects (1.324 vs. 0.6557, respectively) and p-value <0.0001. Conclusion: We investigated that decreased miR-125a-5p expression levels were significantly associated with increased STAT3 expression in BC tissues. Therefore, the expression changes of miR- 125a-5p can be an important potential biomarker for early diagnosis of breast cancer. Also, the miRNA molecule may have serious therapeutic potential.