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Journal of Clinical and
            Translational Research                                            miRNA in pneumonia and pulmonary fibrosis



            practitioners in improving treatment approaches and   et al. highlighted the importance of miRNAs in controlling
            researchers in developing novel therapeutic strategies.  post-transcriptional gene silencing in an S-S manner. They
                                                               highlight the vast network of regulatory RNAs formed by
            2. Evidence from current literature                the miRNAs with multiple targets, which enables flexible

            Randomized controlled trials comparing commonly used   control of mRNA expression, especially in the mammalian
            antibiotics for pneumococci infections with placebo or   nervous system. 17
            other classes of antibiotics in children under 18 years with   Precursor miRNAs are processed in the nucleus and
            community-acquired LRTI secondary to pneumococci   cytoplasm by the endoribonucleases Drosha and Dicer.
            have demonstrated the effectiveness of antibiotics in   The modulation of mature miRNA levels is essential for
                               1
            treating pediatric LRTI.  Although atypical pneumonia has   physiological processes such as development, differentiation,
            been known for more than a century, its main causative   and disease pathogenesis. Post-transcriptional mechanisms
            pathogens are generally  Chlamydia pneumoniae,  M.   include both cis-acting sequences in precursor miRNAs
            pneumoniae, and L. pneumophila. The atypical pathogens   and trans-acting factors that interact with these
            are  estimated  to  account  for  22% of  pneumonia  cases   precursors, affecting their processing.  RNA-binding
            worldwide, with diagnosis largely dependent on laboratory-  proteins (RBPs) play the principal role in controlling the
            based identification methods.Therapy with either macrolide   processing of miRNAs. Recent investigations suggest that

            antibiotics or fluoroquinolones is recommended, but more   innate immune responses, particularly involving estrogen-
            data are though further evidence is required to establish   mediated signaling pathways, may contribute significantly
            optimal treatment strategies. Combination therapy may be   to systemic lupus erythematosus (SLE). Estrogen has been
            considered in severe patients. 4                   shown to lower the activation threshold of immune cells
              Padilla  has described IPF as a chronic liver disease   and boost the expression of  toll-like receptor 8  (TLR8).
            characterized by  interstitial fibrosis, leading to  a   Notably, miR-21 has been detected in exosomes derived
            progressive decline in respiratory function and shortened   from  SLE patient serum and  in vitro experiments have
            life expectancy. Treatment strategies generally range from   shown that pseudoexosomes can stimulate immune cells
                                                                                      13
            disease-modifying interventions to symptomatic relief.   to increase TLR8 expression.
            Significant advances have been made in understanding   3. Biogenesis of miRNA
            its pathogenesis, leading to the development of evidence-
            based therapeutic guidelines.  In October 2014, the U.S.   miRNAs are typically located in the exonic or intronic
                                    6
            Food and Drug Administration approved pirfenidone and   regions of protein-coding genes, as well as in intergenic
            nintedanib for the treatment of IPF. These agents provide   areas. Their production begins with transcription mediated
            clinicians with validated therapeutic options, although   by RNA polymerase II or III, resulting in a primary
            their use requires careful consideration of safety profiles   transcript called pri-miRNA. These pri-miRNAs usually
            and monitoring. 15                                 have a 33-bp  hairpin structure, a terminal loop, and a
                                                               flanking single-stranded sequence. They are also capped at
              Lu and Rothenberg demonstrated that miRNAs – tiny,
            naturally occurring RNA molecules – play critical roles in   the 5’ end and polyadenylated at the 3’ end. In the nucleus,
                                                               the microprocessor complex, consisting of the ribonuclease
            post-transcriptional gene regulation. In allergy research,   Drosha and the RBP DGCR8, processes the pri-miRNA by
            there is a growing interest in miRNAs owing to their   cutting 11 base pairs from the junction of the hairpin stem
            potential as biomarkers. miRNA mimics and inhibitors   and single-stranded RNA. This produces a pre-miRNA,
            have emerged as promising candidates for innovative   which is then transported to the cytoplasm by Exportin-5,
            therapeutic approaches. Advanced technological tools have   a protein that depends on Ran-GTP. In the cytoplasm, the
            been devised for various miRNA-related tasks, including   enzyme Dicer further processes the pre-miRNA by cutting
            isolation, quantification, profiling, target identification,   near the terminal loop to generate the mature miRNA
            and manipulation of mRNA levels in both laboratory   and its complementary strand (miRNA*) acting as the
            settings and within living organisms. 8
                                                               passenger strand. Other associated proteins, such as HIV-1
              miRNAs play a major role in cellular communication   TAR RNA-binding protein (TRBP) and protein activator of
            by binding to  complementary  sequences  in  mRNA,   PKR kinase (PACT), enhance the stability and processing
            leading to the suppression of protein synthesis. However,   efficiency of Dicer. In plants such as Arabidopsis, miRNA
            their function is more complex than simply turning   maturation also proceeds in a stepwise fashion, primarily
            genes on or off.  miRNAs act as post-transcriptional   through the action of Dicer-like 1 (DCL1). Other Dicer-
                          10
            regulators, playing pleiotropic roles in various biological   like proteins (DCL2, DCL3, and DCL4) contribute to the
            functions and diseases, including cancer.  Catalanotto   generation of miRNAs of differing lengths. 18
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            Volume 11 Issue 2 (2025)                        30                         doi: 10.36922/JCTR025080009
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