MicroRNA - Volume 10, Issue 3, 2021

The primate-specific microRNA gene cluster on chromosome 19 (C19MC) is composed of 56 mature microRNAs (miRNAs), which are divided into three subgroups according to the sequence similarity. This cluster is principally expressed in the placenta but not in other tissues. C19MC is involved in the regulation of proliferation, migration, and invasion of trophoblastic cells, which are important for the development of the placenta. There is a growing number of studies that have found an altered expression of some miRNAs of the C19MC cluster in cancer, suggesting that these could play an important role in the development of this disease. Therefore, in this work, we provided an overview of the C19MC cluster's role in cancer through a systematic review of published articles. In particular, we focused on miRNAs of subgroup 3. These studies suggest that miRNAs such as miR-512-3p, miR-512-5p, miR-516a-5p, miR-516b-5p, and miR-498-5p could play a pivotal role in the development of therapies for cancer. Future studies are necessary to elucidate the molecular processes and pathways regulated by subgroup 3 miRNAs.

Oxidative stress influences several physiological and pathological cellular events, including cell differentiation, excessive growth, proliferation, apoptosis, and inflammatory response. Therefore, oxidative stress is involved in the pathogenesis of various diseases, including pulmonary fibrosis, epilepsy, hypertension, atherosclerosis, Parkinson’s disease, cardiovascular disease, and Alzheimer’s disease. Recent studies have shown that several microRNAs (miRNAs) are involved in the development of various diseases caused by oxidative stress and that miRNAs may be useful to determine the inflammatory characteristics of immune responses during infection and disease. In this review, we describe the known effects of miRNAs on reactive oxygen species to induce oxidative stress and miRNA regulatory mechanisms involved in the uncoupling of Keap1-Nrf2 complexes. Finally, we summarized the functions of miRNAs in several antioxidant genes. Understanding the crosstalk between miRNAs and oxidative stress-inducing factors during physiological and pathological cellular events may have implications for the design of more effective treatments for immune diseases.

MicroRNAs (miRNAs) are highly conserved non-coding RNAs involved in many physiological processes such as cell proliferation, inhibition, development of apoptosis, differentiation, suppression of tumorigenicity, and regulation of cell growth. The description of the alterations of miRNA expression patterns in cancers will be helpful in recognizing biomarkers for early detection and possible therapeutic intervention in the treatment of cancers. Recent studies have shown that miR-451 is broadly dysregulated in lung cancer and is a crucial agent in lung tumor progression. This review summarizes recent advances in the potential role of miR-451 in lung cancer diagnosis, prognosis, and treatment and provides an insight into the potential use of miR-451 for the development of advanced therapeutic methods in lung cancer.

Background: Several studies have reported a possible association of miR-146a rs2910164 polymorphism with Breast Cancer (BC) development. However, the correlation between this polymorphism and susceptibility to BC is under debate. The current meta-analysis was designed and performed to more conclusively evaluate the miR-146a rs2910164 polymorphism and its potential link to BC. Methods: Our team has selected eligible studies (published up to October 2, 2020) from several electronic databases, including Web of Science, PubMed, Scopus and Google Scholar. A total number of 9,545 BC cases and 10,030 controls extracted from 26 eligible articles were included in this study. We utilized pooled Odds Ratios (ORs) as well as 95% confidence intervals (95% CIs) under five genetic models for quantitative estimation of any possible association between miR-146a rs2910164 polymorphism and BC. Results: Based on this meta-analysis, our findings suggest that there is no significant association between miR-146a rs2910164 polymorphism and BC risk. However, stratified analysis revealed that the rs2910164 polymorphism significantly increased the risk of BC in hospital-based studies using the homozygous genetic model (OR=1.37, 95%CI=1.01-1.86, p=0.043, CC vs. GG). Neither Asian nor Caucasian populations showed any significant association between rs2910164 polymorphism and BC susceptibility. Conclusion: In summary, our findings suggest that BC development is not associated with miR-146a rs2910164 polymorphism. However, larger ingenious future investigations might be needed for a more precise estimation of any association between miR-146a rs2910164 polymorphism and BC.

Background: Insulin resistance is a condition in which the body produces insulin but is unable to use it effectively. Aberrations in insulin signaling are known to play a crucial role in the pathogenesis of this disease state. Eventually, patients will have glucose build-up in their blood instead of being absorbed by the cells, leading to type 2 diabetes. Objective: In the current study, we focus on understanding the role of rSNP mediated miRNA:mRNA dysregulation and its impact on the above metabolic condition. Methods: More than 30 genes involved in the insulin signaling pathway were found using the KEGG database. The 3’UTR end of genes was studied by using RegRNA and Ensembl, whereas TargetScan along with miRbase were used to identify their target miRNAs. Binding free energy was used as a parameter to analyze the effect of polymorphism on the miRNA:mRNA duplex formation. Further, the UNA fold was used to determine the heat capacity changes. Results: The genes INSR, INS, GLUT4, FOXO1, IL6, TRIB3, and SREBF1, were selected for analysis. Multiple miRNAs, hsa-miR-16-5p, hsa-miR-15a-15p were identified in the SNP occurring region for INSR. INS, too, showed similar results. INSR, INS, and TRIB3 were found to have the maximum change in their binding free energy due to rSNP variation. A destabilisation in the heat capacity values was observed too, which contributed due to rSNP induction. Conclusion: A direct relationship between miRNA target polymorphism and the stability of the miRNA:mRNA duplex was observed. The current methodology used to study insulin resistance pathogenesis could elaborate on our existing knowledge of miRNA-mediated disease states.

Background: Breast cancer, being a heterogenous disease at the intra-tumoral and intertumoral levels, presents challenges in following the progress of the disease. Tumour-secreted aberrantly expressed miRNAs obtained from peripheral blood represent a non-invasive alternative resource for detecting and monitoring the development of the disease. This study evaluates the expression of miR-155, miR-133a, miR-21 and miR-205 as non-invasive, prognostic and follow-up markers for breast cancer. Methods: Plasma expression levels of miR-155, miR-133a, miR-21 and miR-205 were measured using real-time PCR in breast cancer patients (n=63) at presentation, healthy controls (n=25), and in post-treatment samples of 31 patients. A meta-analysis was performed using 43 studies identified from PubMed, Google Scholar and Scopus databases. Hedge’s g values were used to calculate the overall effect size. Results: Plasma miR-21 levels were higher in breast cancer patients at presentation compared to controls, while no difference was observed for miR-155, miR-133a and miR-205. These results were further supported by the meta-analysis. The altered levels of miR-155 during tamoxifen treatment indicated a potential role for miR-155 in monitoring treatment response. Further, high expressions of at least three miRNAs correlated with poor overall survival in the breast cancer patients. Conclusion: Plasma levels of miR-155, miR-133a, miR-21 and miR-205 may be useful as prognostic and follow-up markers for breast cancer with further validation in a large cohort of patients.

Background: The prevalence of Cervical Cancer (CC) is disproportionately higher in developing countries. It is the second most frequent cancer type among Bangladeshi women and the major cause of morbidity and mortality. However, no previous data reported the association of miR-218-2 gene polymorphisms in Bangladeshi cervical cancer patients. Aim: This case-control study was designed to find the link between the rs11134527 polymorphism in miR-218-2 and CC. Methods: A total of 488 subjects were recruited, comprising 256 cervical cancer patients and 232 healthy females. Genotyping was conducted with the tetra-primer ARMS-PCR technique to detect the association. Results: The results of genotype data showed that rs11134527 was in the Hardy-Weinberg equilibrium in both CC cases and controls (P >0.05). Overall, the polymorphism was found to be significantly associated with an increased risk of cervical cancer with AG genotype (AG vs. GG: OR = 2.26, 95% Cl = 1.40-3.66, P = 0.0008), AA genotype (AA vs. GG: OR = 3.64, 95% Cl = 2.17-6.10, P <0.0001), dominant model (AG+AA vs. GG: OR = 2.75, 95% Cl = 1.75-4.31, P <0.0001), recessive model (AA vs. GG+AG: OR = 2.08, 95% Cl = 1.41-3.08, P = 0.0002), and A allele (A vs. G: OR = 1.94, 95% Cl = 1.51-2.51, P <0.0001). All of these correlations remained statistically significant after performing Bonferroni correction (P <0.008). Conclusion: Our study suggests that the rs11134527 polymorphism in the miR-218-2 gene contributes to the susceptibility of CC in Bangladeshi women.