MicroRNA - Volume 10, Issue 1, 2021

The mulberry silkworm Bombyx mori, apart from its well-known economic importance, has also emerged as an insect model to study host-pathogen interactions. The major concern for silkworm cultivation and the sericulture industry is the attack by various types of pathogens mainly including viruses, fungi, bacteria and protozoa. Successful infection requires specific arsenals to counter the host immune response. MicroRNAs (miRNAs) are one of the potential arsenals which are encoded by viruses and effectively used during host-pathogen interactions. MiRNAs are short noncoding 19-25 nucleotides long endogenous RNAs that post-transcriptionally regulate the expression of protein-coding genes in a sequence-specific manner. Most of the higher eukaryotes encode miRNAs and utilize them in the regulation of important cellular pathways. In silkworm, promising functions of miRNAs have been characterized in development, metamorphosis, immunity, and host-pathogen interactions. The viral miRNA-mediated fine-tuning of the viral, as well as cellular genes, is beneficial for making a cellular environment favorable for the virus proliferation. Baculovirus and cypovirus, which infect silkworm have been shown to encode miRNAs and their functions are implicated in controlling the expression of both viral and host genes. In the present review, the author discusses the diverse functions of viral-encoded miRNAs in evasion of the host immune responses and reshaping of the silkworm cellular environment for replication. Besides, a basic overview of miRNA biogenesis and mechanism of action is also provided. Our increasing understanding of the role of viral miRNAs in silkworm-virus interactions would not only assist us to get insights into the intricate pathways but also provide tools to deal with dreaded pathogens.

Specific microRNA (miRNA) expression profiles have been reported to be predictive of specific clinical outcomes of dental implants and might be used as biomarkers in implant dentistry with diagnostic and prognostic purposes. The aim of the present narrative review was to summarize current knowledge regarding the use of miRNAs in implant dentistry. The authors attempted to identify all available evidence on the topic and critically appraise it in order to lay the foundation for the development of further research oriented towards the clinical application of miRNAs in implant dentistry.

MicroRNAs (miRNAs) are non-coding RNAs ranging from 18-24 nucleotides, also known to regulate the human genome mainly at the post-transcriptional level. MiRNAs were shown to play an important role in most biological processes such as apoptosis and in the pathogenesis of many diseases such as cardiovascular diseases and cancer. Recent developments of advanced molecular high-throughput technologies have enhanced our knowledge of miRNAs. MiRNAs can now be discovered, interrogated, and quantified in various body fluids serving as diagnostic and therapeutic markers for many diseases. While most studies use blood as a sample source to measure circulating miRNAs as possible biomarkers for disease pathogenesis, fewer studies have assessed the role of salivary miRNAs in health and disease. This review aims at providing an overview of the current knowledge of the salivary miRNome, addressing the technical aspects of saliva sampling, and highlighting the applicability of miRNA screening to clinical practice.

Background: Although the protein-coding genes are subject to histone hyperacetylation- mediated regulation, it is unclear whether microRNAs are similarly regulated in the T cell leukemia Jurkat. Objective: To determine whether treatment with the histone modifier Trichostatin A could concurrently alter the expression profiles of microRNAs and protein-coding genes. Methods: Changes in histone hyperacetylation and viability in response to drug treatment were analyzed, respectively, using western blotting and flow cytometry. Paired global expression profiling of microRNAs and coding genes was performed and highly regulated genes have been validated by qRT-PCR. The interrelationships between the drug-induced miR-494 upregulation, the expression of putative target genes, and T cell receptor-mediated apoptosis were evaluated using qRT-PCR, flow cytometry, and western blotting following lipid-mediated transfection with specific anti-microRNA inhibitors. Results: Treatment of Jurkat cells with Trichostatin A resulted in histone hyperacetylation and apoptosis. Global expression profiling indicated prominent upregulation of miR-494 in contrast to differential regulation of many protein-coding and non-coding genes validated by qRT-PCR. Although transfection with synthetic anti-miR-494 inhibitors failed to block drug-induced apoptosis or miR-494 upregulation, it induced the transcriptional repression of the PVRIG gene. Surprisingly, miR-494 inhibition in conjunction with low doses of Trichostatin A enhanced the weak T cell receptor- mediated apoptosis, indicating a subtle pro-survival role of miR-494. Interestingly, this prosurvival effect was overwhelmed by mitogen-mediated T cell activation and higher drug doses, which mediated caspase-dependent apoptosis. Conclusion: Our results unravel a pro-survival function of miR-494 and its putative interaction with the PVRIG gene and the apoptotic machinery in Jurkat cells.

Background: Ovarian cancer is the most deadly cancer that requires novel diagnostics and therapeutics. MicroRNAs are viewed as essential gene regulatory elements involved in different pathobiological mechanisms of many cancers, including ovarian cancer. Objective: This study examined the relationship between microRNA (miRNA) expression and response to platinum-based chemotherapy. Methods: Genome-wide miRNA expression analysis was conducted using Epithelial Ovarian Cancer (EOC) tissues from 25 patients with 17 malignant tumors and eight benign ovarian tumors. Candidate miRNAs that respond to platinum-based chemotherapy were selected for validation by quantitative RT-PCR. Results: Among 2,578 mature human miRNAs, high expression of miR-483-5p correlated with poor responses to platinum-based chemotherapy in EOC patients. Furthermore, high levels of miR-483-5p in the resistant group suppressed expression of the apoptotic regulator TAOK-1. Conclusion: A possible marker for the prediction of chemotherapy response and resistance in patients may be miR-483-5p. Choosing the right treatment for each patient with EOC can avoid the risk of developing chemotherapy resistance.

Background: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease. Objective: We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease. Methods: MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured. Results: ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage. Conclusion: miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Background: MicroRNAs (miRNAs), as tissue specific regulators of gene transcription, may be served as biomarkers for Colorectal Cancer (CRC). Objective: This study aimed to investigate the potential role of the cancer-related hsa-miRNAs as biomarkers in Colon Cancer (CC) and Rectal Cancer (RC). Methods: A total of 148 CRC samples (74 rectum and 74 colon) and 74 adjacent normal tissues were collected to examine the differential expression of selected ten hsa-miRNAs using quantitative Reverse Transcriptase PCR (qRT-PCR). Results: The significantly elevated levels of miR-21, miR-133b, miR-18a, miR-20a, and miR-135b, and decreased levels of miR-34a, miR-200c, miR-145, and let-7g were detected in colorectal tumors compared to the healthy tissues (P<0.05). Hsa-miR-20a was significantly overexpressed in rectum compared to colon (p =0.028) from a cut-off value of 3.15 with a sensitivity of 66% and a specificity of 60% and an AUC value of 0.962. Also, hsa-miR-145 was significantly overexpressed in colon compared to the rectum (p =0.02) from a cut-off value of 3.9 with a sensitivity of 55% and a specificity of 61% and an AUC value of 0.91. Conclusion: In conclusion, hsa-miR-20a and hsa-miR-145, as potential tissue-specific biomarkers for distinguishing RC and CC, improve realizing the molecular differences between these local tumors.

Background: Squamous Cell Carcinoma (SCC) includes more than 90% of malignancies of the oral cavity. Early diagnosis could effectively improve patients' quality of life and treatment outcomes of oral cancers. MicroRNAs as non-encoding genes have great potential to initiate or suppress cancer progression. Recent studies have shown that disruption of micro-RNA regulation is a common occurrence in cancers. Objective: This study set out to evaluate the expression of microRNA-15a (miR-15a) and microRNA- 16-1 (miR-16-1) in the saliva of Oral Squamous Cell Carcinoma (OSCC) patients in comparison with a healthy control group. Methods: This case-control study was performed on fifteen patients with OSCC and fifteen healthy volunteers as the control group. A 5 ml of non-stimulating whole saliva was collected by spitting method from patients and controls and stored at -70°C. The expression of miR-15a and miR-16-1 was investigated using quantitative Reverse-Transcription Polymerase Chain Reaction (RT-qPCR). Results: MiR-15a and miR-16-1 were downregulated in OSCC patients compared with the control group (p<0.001). The sensitivity of miR-15a and miR-16-1 in differentiating OSCC patients from healthy individuals was 93.3% and 86.67%, respectively, and their specificity was 86.67% and 92.33%, respectively. The diagnostic accuracy of miR-15a was 90%, and miR-16-1 was 93.3%. Conclusion: The present study showed a decrease in the relative expression of miR-15a and miR-16-1 in OSCC patients compared with healthy individuals. It is probable to introduce salivary values of miR-15a and miR-16-1 as a non-invasive tool for early detection of OSCC. Decreased expression of miR-15a and miR-16-1 in OSCC indicates the possible effective role of these genes in OSCC etiopathogenesis.