MicroRNA - Volume 13, Issue 1, 2024

Background: Micro-RNAs are endogenous non-coding RNA moieties of 22-27 nucleotides that play a crucial role in the regulation of various biological processes and make them useful prognostic and diagnostic biomarkers. Discovery and experimental validation of miRNA is a laborious and time-consuming process. For early prediction, multiple bioinformatics databases are available for miRNA target prediction; however, their utility can confuse amateur researchers in selecting the most appropriate tools for their study. Objective: This descriptive review aimed to analyse the usability of the existing database based on the following criteria: accessibility, efficiency, interpretability, updatability, and flexibility for miRNA target prediction of 3’UTR of mRNA in diverse species so that the researchers can utilize the database most appropriate to their research. Methods: A systematic literature search was performed in PubMed, Google Scholar and Scopus databases up to November 2022. ≥10,000 articles found online, including 129;“130 miRNA tools, which contain various information on miRNA. Out of them, 31 databases that provide information on validated 3'UTR miRNAs target databases were included and analysed in this review. Results: These miRNA database tools are being used in varied areas of biological research to select the most suitable miRNA for their experimental validation. These databases, updated until the year 2021, consist of miRNA-related data from humans, animals, mice, plants, viruses etc. They contain 525-29806351 data entries, and information from most databases is freely available on the online platform. Conclusion: Reviewed databases provide significant information, but not all information is accurate or up-to-date. Therefore, Diana-TarBase and miRWalk are the most comprehensive and up-to-date databases.

Long non-coding RNA [LncRNA] dysregulation has been seen in many human cancers, including several kinds of leukemia, which is still a fatal disease with a poor prognosis. LncRNAs have been demonstrated to function as tumor suppressors or oncogenes in leukemia. This study covers current research findings on the role of lncRNAs in the prognosis and diagnosis of leukemia. Based on recent results, several lncRNAs are emerging as biomarkers for the prognosis, diagnosis, and even treatment outcome prediction of leukemia and have been shown to play critical roles in controlling leukemia cell activities, such as proliferation, cell death, metastasis, and drug resistance. As a result, lncRNA profiles may have superior predictive and diagnostic potential in leukemia. Accordingly, this review concentrates on the significance of lncRNAs in leukemia progression based on their chromosomal position.

Introduction: To retrieve, and classify PCa miRNAs and identify the functional relationship between miRNAs and their targets through literature collection with computational analysis. Background: MicroRNAs play a role in gene regulation, which can either repress or activate the gene. Hence, the functions of miRNAs are dependent on the target gene. This study will be the first of its kind to combine computational analysis with corpus PCa data. Effectively, our study reported the huge number of miRNAs associated with PCa along with functional information. Objective: The identification and classification of previously known full PCa miRNAs and their targets were made possible by mining the literature data. Systems Biology and curated data mining assisted in identifying optimum miRNAs and their target genes for PCa therapy. Methods: PubMed database was used to collect the PCa literature up to December 2021. Pubmed. mineR package was used to extract the microRNAs associated articles and manual curation was performed to classify the microRNAs based on the function in PCa. PPI was constructed using the STRING database. Pathway analysis was performed using PANTHER and ToppGene Suite Software. Functional analysis was performed using ShinyGO software. Cluster analysis was performed using MCODE 2.0, and Hub gene analysis was performed using cytoHubba. The genemiRNA network was reconstructed using Cytoscape. Results: Unique PCa miRNAs were retrieved and classified from mined PCa literature. Six hundred and five unique miRNAs from 250 articles were considered as oncomiRs to trigger PCa. One hundred and twenty unique miRNAs from 118 articles were considered Tumor Suppressor miRNAs to suppress the PCa. Twenty-four unique miRNAs from 22 articles were utilized as treatment miRNAs to treat PCa. miRNAs target genes and their significant pathways, functions and hub genes were identified. Conclusion: miR-27a, miR-34b, miR-495, miR-23b, miR-100, miR-218, Let-7a family, miR-27a- 5p, miR-34c, miR-34a, miR-143/-145, miR-125b, miR-124 and miR-205 with their target genes AKT1, SRC, CTNNB1, HRAS, MYC and TP53 are significant PCa targets.

Background: Colorectal cancer (CRC) is the third most common cancer in the world. Noncoding RNAs or microRNAs (miRNAs; miRs) biomarkers can play a role in cancer carcinogenesis and progression. Specific KRAS and EGFR mutation are associated with CRC development playing a role in controlling the cellular process as epigenetic events. Circulating serum miRs can serve for early diagnosis, monitoring, and prognosis of CRC as biomarkers but it is still unclear, clinically. Objective: To determine potential biomarkers of circulating serum miR-133b and miR-206 in CRC patients Methods: Bioinformatic prediction of microRNA was screened followed by TargetScanHuman7.2, miRTar2GO, miRDB, MiRanda, and DIANA-microT-CDS. Forty-four CRC serum (19 locally advanced, 23 distant advanced CRC) and 12 normal serum samples were subsequently extracted for RNA isolation, cDNA synthesis, and miR validation. The candidate circulating serum miR-133b and miR-206 were validated resulting in a relative expression via quantitative RT-PCR. Relative expression was normalized to the spike-internal control and compared to normal samples as 1 using the -2ΔΔCt method in principle. Results: Our results represented 9 miRs of miR-206, miR-155-5p, miR-143-3p, miR-193a-3p, miR-30a- 5p, miR-30d-5p, miR-30e-5p, miR-543, miR-877-5p relate to KRAS-specific miRs, whereas, 9 miRs of miR-133b, miR-302a-3p, miR-302b-3p, miR-302d-3p, miR-302e, miR-520a-3p, miR-520b, miR-520c- 3p and miR-7-5p relevance to EGFR-specific miRs by using the bioinformatic prediction tools. Our results showed a decreased expression level of circulating serum miR-133b as well as miR-206 associating with CRC patients (local and advanced metastasis) when compared to normal (P < 0.05), significantly. Conclusion: The circulating serum miR-133b and miR-206 can serve as significant biomarkers for monitoring the clinical outcome of progression with metastatic CRC patients. Increased drug-responsive CRC patients associated with crucial molecular intervention should be further explored, clinically.

Background: Alteration in the expression and activity of drug-metabolizing enzymes (DMEs) can alter the pharmacokinetics and hence the response of the drug. Some chemicals found in herbs and fruits affect the expression of DMEs. Calamintha incana is commonly used in Middle Eastern Arabic countries. There is no report regarding the influence of Calamintha incana on the hepatic expression of DMEs. Aims: The current investigation aimed to investigate the effect of Calamintha incana consumption on the mRNA expression of major hepatic drug-metabolizing cytochrome (cyp) P450 genes in mice. Methods: The chemical composition of the ethanoic extract was analyzed using liquid chromatography/ mass spectrometry. Then, 21 BALB/c mice were used for the in vivo experiment. The mice were divided into three groups, each consisting of seven mice. The first group (low-dose group) was treated with 41.6 mg/kg of Calamintha incana extract and the second group was administered the high-dose (125 mg/kg) of the extract for one month. The mice in the third “control” group administrated the vehicle 20% polyethylene glycol 200. Then, the expression of cyp3a11, cyp2c29, cyp2d9, and cyp1a1 was analyzed using the real-time polymerase chain reaction. The relative liver weights of the mice and the hepatic pathohistological alterations were assessed. Results: The ethanolic extract of Calamintha incana contained 27 phytochemical compounds. The most abundant compounds were linolenic acid, myristic acid, and p-cymene. It was found that the low dose of Calamintha incana extract upregulated significantly (P < 0.05) the expression of cyp3a11 by more than ten folds in the liver of treated mice. Furthermore, the histological analysis showed that low- and high-dose administration of the C. incana did not cause pathological alterations. Conclusion: It can be concluded from these findings that consumption of low doses of Calamintha incana upregulated the mRNA expression of mouse cyp3a11 without causing histopathological alterations in the livers. Further studies are needed to determine the influence of Calamintha incana on the pharmacokinetics and response of drugs metabolized by cyp3a11.

Background: Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. Methods: We have deployed miRge for microRNA analysis, DESeq for differential expression analysis, and Cytoscape for competing endogenous RNA network investigation. Results: Here, we identified 76 miRNAs that were differentially expressed in DCIS and IDC. Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in earlystage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples. Conclusion: Higher expression of miR-301a-3p is associated with poor overall survival in The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.