MicroRNA - Volume 5, Issue 2, 2016

MicroRNAs (miRNAs) are small and important RNA molecules. They can regulate gene expression at different levels. Although their biogenesis has been well documented, elucidation of miRNA-dependent activation of mRNA translation has just begun. Here, we highlighted different patterns of miRNA-dependent activation of mRNA translation: miRNA can activate mRNA translation through binding different target sites; in different sub-cellular locations; under different cellular circumstances. MiRNA-dependent activation of mRNA translation suggests unexpected functions of miRNA, that could provide new clues in functional studies of other ncRNAs.

B-cell lymphomas represent a heterogeneous collection of more than twenty-five different malignancies. Classification is often challenging as primarily based upon, sometimes subjective, histopathological criteria and misdiagnosis can result in inappropriate treatment decisions. MicroRNAs (miRNAs) hold great promise as novel biomarkers (diagnostic, prognostic and predictive) of B-cell lymphoma in addition to being potential therapeutic targets. The most promising of these miRNAs more often than not play key regulatory roles in lymphopoiesis (development of lymphocytes) when under physiological conditions, and in the pathology of lymphoid malignancies when aberrantly expressed. In this review we consider the identity and functional role of miRNAs in the most common forms of B-cell lymphomas, their role in lymphopoiesis and their potential as biomarkers for these malignancies.

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adult population in western country. In the last decade, several findings have substantially revolutionized the old concept that CLL is a disease originating from mature, not-dividing cell with indolent clinical course. Notably, next generation sequencing (NGS) has contributed to deepen the knowledge of the cellular networks that imply the onset and the progression of CLL. Among genetic aberrations that are recurrently observed in B-cells from patients with CLL, microRNA deregulation represented the first epigenetic mechanism that has been identified. Through epigenetic mechanism they can modulate gene expression and interfere with cellular pathways that are involved in cell cycle, apoptosis and B-cell receptor (BCR) activation. Although few studies have shown the prognostic and predictive value of microRNA expression levels, their validation within prospective clinical trials is warranted.

microRNAs (miRNAs) are small noncoding RNAs able to suppress gene expression by targeting messenger RNAs for translational repression or, at lesser extent, degradation. miRNAs are widely expressed in tissues and organs and play fundamental roles in controlling cell proliferation, apoptosis, differentiation, cell migration, autophagy and metabolism. Uncontrolled expression of miRNAs has been associated with cancer progression, and miRNA up- or down-regulation has been linked to oncogenic and tumor-suppressive roles in cancers such as breast cancer, colorectal cancer, lung cancer, gastric cancer and glioblastoma. Altered expression of the miRNA mir-25 has been reported in many human malignant tumors, participating in various cellular processes accordingly with its broad range of potential mRNAs target. In the present review, we briefly discuss the mechanisms underlying miR-25-mediated tumorigenesis in six different human cancers and its possible future as a potential diagnostic and prognostic parameter as well as therapeutic target in clinical applications.

MicroRNAs (miRNAs) are non-coding RNA molecules, with sequence length of 19-24 nucleotides, which can induce mRNA degradation and regulate protein translation repression. Recently plenty of reports showed that miRNAs increase or decrease in the serum (circulating miRNAs) and in PBMC of Human immunodeficiency virus type 1 (HIV-1) infected individuals to affect the replication of HIV-1 through regulating HIV-1 proteins or HIV-1 replication related host factors. Many of miRNAs can suppress HIV-1 replication, but do not affect the integrated viral DNA. Low or no viral protein expression could result in a block of virus and its replication to induce HIV-1 latency, which is the great obstacle of the cure of HIV-1 infection. In the HIV-1 latency reservoir, the integrated provirus can reactivate under appropriate stimulus, which results in HIV-1 reproduction. Factors imply that cellular miRNAs may promote the establishment of HIV-1 latency. Further studies on the mechanisms of miRNAs affecting viral protein expression will provide new approaches to clear the viral reservoir.

Background: Abdominal aortic aneurysm (AAA) is usually asymptomatic and mostly diagnosed incidentally. Aortic dilatation progresses along with the wall weakening and eventually leads to a life-threatening rupture. Currently, there are no effective screening biomarkers for AAA. MicroRNAs, a class of small noncoding RNA molecules, offer great potential as biomarkers because of their stability in the bloodstream and expression profile specific for different diseases. Objective: To assess the circulating miR-29c-3p as a potential biomarker of AAA and to elucidate the biological functions of miR-29c-3p in terms of pathogenesis of aneurysms. Methods: Two groups of patients scheduled for elective surgery were studied: 52 patients with AAA, and 51 patients with peripheral artery disease who served as a control group (matched by age and gender). Serum miRNA was measured for circulating miR-29c-3p using quantitative real-time PCR. Functional tests of miR-29c-3p impact on the targeted transcripts were studied using its mimic or inhibitor and a cell culture of endothelial cells. Results: Serum miR-29c-3p was significantly elevated in AAA patients as compared with controls (RQ=8.73) and correlated with the diameter of the aneurysm. No association between well-known risk factors and level of circulating miR-29c-3p was found using a logistic regression. In vitro study revealed that miR-29c-3p suppressed transcripts of ELN, COL4A1, PTEN and VEGFA. Conclusion: The results suggest that elevated miR-29c-3p is a potential serum biomarker for AAA. Causal involvement of miR-29c-3p in pathogenesis of the disease was found in human vascular endothelial cells, which extracellular matrix synthesis and integrity maintenance was inhibited.

MicroRNAs (miRNAs) are non-coding RNAs that are involved in various biological pathways by regulating gene expression. Teeth develop via reciprocal and sequential interactions between the epithelium and the ectomesenchyme. The specific functions of several genes during tooth development are known, and the involvement of their mutations in the pathogenesis of congenital dental defects has been widely studied. The miRNA pathway is considered to have a significant role in embryogenesis including tooth development. It has been shown that miRNAs regulate morphogenesis of tooth by fine-tuning the signalling networks, however, their precise role in tooth differentiation and morphogenesis is still elusive. The present review focuses on the studies that have used animal models to explore the function of miRNAs in tooth development. Major findings with special emphasis on the miRNA involvement in fine-tuning and network regulation are presented and discussed. Disturbances in tooth development in the global miRNA processing knockouts mirror the essential fine-tuning guiding appropriate formation of dental hard tissues. However, further investigation of single miRNA function and mutation, including deletion and overexpression, may lead to improved knowledge on development of particular dental defects in humans. In the light of similarities between tooth development and other organs originating from the epithelium, further understanding of miRNAs` function during tooth development may have wide biological relevance.

Background: MicroRNAs (miRNAs) are non-coding RNAs known to control a broad range of biological functions such as cellular proliferation, differentiation and programmed cell death. Recent reports showed that miRNAs can act as oncogenes or tumor suppressors, thereby, playing an important role in cancer initiation and progression. Moreover, we know that Expressed sequence tags (ESTs) are random single pass sequence reads, which displays the condition/tissue specific transcripts (coding and non-coding) of an organism. Methods: In the present study, we have applied the bioinformatics approach to identify miRNA from prostate cancer using EST resource and its expressions were analyzed by quantitative reverse transcription PCR (qRT-PCR). Results: Analysis of transcriptomics resource from the LNCaP cells revealed the presence of an EST encoding hsa-miR-3654. Presence of the premature candidate of miR-3654, demonstrates its expression in LNCaP cells. We further indentified that the expression level (Fold Induction) of miR-3654 in LNCaP was higher than the normal and androgen insensitive prostate cancer cell lines (PNT1A, PC-3). Conclusion: we have identified the miR-3654 involved in prostate cancer progression using computational approach and hypothesized that the down regulation of miR-3654 could be responsible for a solid tumor to get cancer stem-like cell phenotype. Further studies are required to investigate the molecular mechanisms behind the STAT3 mediated miR-3654 repression and the associated metastasis.

Background: Artificial microRNAs (miRNAs) are designed to develop an RNAi-based gene therapy. Recently, it has been suggested that the flanking sequences and terminal loop structure play a critical role in RNAi biogenesis and target recognition, but no extensive study regarding the different miRNA backbone for artificial miRNAs optimization has been conducted. Objective: We tested three artificial miRNAs with human hsa-miR30a (common miRNA), hsa-miR150 (T cell specific miRNA), and hsa-miR122 (liver specific miRNA) backbones in HEK-293T and Jurkat cell lines. Methods: Artificial miRNA processing and knockdown efficiency were analyzed by stem-loop RT-PCR, qRT-PCR, luciferase assay and target challenging. Results: We identified strikingly different RNAi activities among these different artificial miRNAs. Our results demonstrated that expression and function of art-miR150 was more than art-miR30 and artmiR122 in both HEK-293T and Jurkat cell lines. Since the main difference in these artificial miRNAs was flanking sequences and terminal loop structure, the change between the expression and function of artificial miRNAs can be attributed to these structures. Conclusion: This study showed that expression of cell-specific artificial miRNA in target and nontarget cells is not different, but variation in flanking sequences and terminal loop can be involved in expression and function of artificial miRNAs. These results can be important for improving artificial miRNA design in RNAi-based gene therapy.

Objective: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3´-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. Methods: We genotyped NOD2 rs3135500 [3´ untranslated region (UTR) A/G] and IL12B rs1368439 (3´UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. Results: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). Conclusion: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.