The regulation of p53 is complicated and remains elusive. An expanded role of p53 in the modulation of microrna expression. Mar 29, 2010 an important morphological feature of vsmcs migrating in vitro is a membrane structure called a podosome gimona et al. Similarly, the p53 tumor suppressor gene is the most frequently mutated gene in human cancer, and its loss or mutation leads to tumor formation in mice. This file contains supplementary figures 118 with legends and. Control of microrna maturation by p53 tumor suppressor and. Additionally, tp53 can activate the processing of specific mirs, such as mir1433p 55, 56, which was on our list. Possible role of tocopherols in the modulation of host microrna with potential antiviral activity in patients with hepatitis b virusrelated persistent infection.
The induction of microrna16 in colon cancer cells by protein. A study on effect of oxaliplatin in microrna expression in. Increased exosomal microrna 21 and microrna 146a levels in the cervicovaginal lavage specimens of patients with cervical cancer previous article in journal an improved mlvf method and its comparison with traditional mlvf, spa typing, mlstscc mec and pfge for the typing of methicillinresistant staphylococcus aureus. Acetylation of p53 stimulates mirna processing and determines cell. Micrornas mirnas are involved in multiple biological activities as well as disease progression including cancer. The p53 is an important regulator in the process of cell apoptosis. The induction of microrna16 in colon cancer cells by. In this study, we used a highthroughput luciferase reporter screen to demonstrate that p53 can be regulated by microrna 1285 mir1285. B p65 regulates microrna224 transcription in mouse ovarian granulosa cells, molecular and cellular endocrinology on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at. As a result, these mrna molecules are silenced, by one or more of the following. Jul 19, 2019 the p53 is an important regulator in the process of cell apoptosis. A model for p53dependent mirnamediated repression of gene expression.
These findings suggest that transcriptionindependent modulation of mirna. May 28, 2010 the wellknown tumor suppressor p53 plays critical roles in the modulation of multiple cellular processes. Microrna control of podosome formation in vascular smooth. Overexpression of these p53 induced mirnas mir16, mir103, mir143, mir145, mir26a and mir206 decreases the rate of cell proliferation. Suzuki hi et al 2009 modulation of microrna processing by p53. Regulation of mirna biogenesis as an integrated component of. Read transcriptional cooperation between p53 and nf. Microrna response to dna damage europe pmc article europe pmc. In this study, we used a highthroughput luciferase reporter screen to demonstrate that p53 can be regulated by microrna1285 mir1285. Since then, hundreds of micrornas have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. The modulation was partly different from that of p53, indicative of a mirna regulatory role of p73 in part distinct from p53. Microrna response to dna damage europe pmc article. Microrna control of p53 juan liu, cen zhang, yuhan zhao, and zhaohui feng department of radiation oncology, rutgers cancer institute of new jersey, rutgers, state university of new jersey, new brunswick 08903, new jersey abstract tumor suppressor p53 plays a. Integrated analysis of microrna and mrna expression and.
We used mirseq to investigate the modulation of mir expression in two independent, donor and. Micrornas mirnas are small noncoding rna transcripts that affect various cellular pathways by serving as regulators of gene expression at the translational and transcriptional level. Microrna21 mir21 is overexpressed virtually in all human cancers and displays oncogenic activity in a transgenic murine model. However, the role of mirna in osteoblast mechanotransduction remains to be. Histone deacetylase 1 enhances microrna processing via. Suzuki hi, yamagata k, sugimoto k, iwamoto t, kato s, et al. Regulation of microrna expression and function by nuclear. India is rich in plant biodiversity, and that has been utilized extensively in traditional medicine. Micrornas mirnas are a class of small, noncoding rnas critically involved in a wide spectrum of normal and pathological processes of cells or tissues by finetuning the signals important for stem cell development, cell differentiation, cell cycle regulation, apoptosis, and transformation. The p53 tumour suppressor is a well known transcriptional activator with many growth suppressive targets. The two riiids form an intramolecular dimer to create one processing center containing two catalytic sites. An important morphological feature of vsmcs migrating in vitro is a membrane structure called a podosome gimona et al. Huarte m, guttman m, feldser d, garber m, koziol mj, kenzelmannbroz d. These findings suggest that transcriptionindependent modulation of mirna biogenesis is intrinsically embedded in a tumour suppressive program governed by p53.
As a service to our customers we are providing this early version of the manuscript. Our aim is to investigate in depth the regulation of microrna expression by hypoxia in the breast cancer cell line mcf7, establish the relationship between microrna expression. Overview of microrna processing, from transcription to the formation of the effector complex. Breast cancer 1 brca1 is a human tumor suppressor gene that plays critical roles in maintenance of genomic stability huen et al. Jul 23, 2009 the p53 tumour suppressor is a well known transcriptional activator with many growth suppressive targets. Transcriptional activation of mir34a contributes to p53mediated apoptosis. Modulation of microrna processing by p53 article pdf available in nature 4607254.
Jan 06, 2012 suzuki hi et al 2009 modulation of microrna processing by p53. Modulation of primirna processing by other transcriptional regulators. Jul 15, 2011 yang w, chendrimada tp, wang q, higuchi m, seeburg ph, shiekhattar r, nishikura k 2006 modulation of microrna processing and expression through rna editing by adar deaminases. Brca1 regulates microrna biogenesis via the drosha. It plays an important role in cell senescence in most murine tissues. Surprisingly, however, mouse genetic studies revealed that mutant p53 is inherently labile, similar to its wild type wt counterpart. While their roles have been attracting more attention in connection with tumor development, the mechanisms. These findings have prompted a great deal of investigation into. Modulation of microrna processing by p53 pubmed result. Most p53 mutations found in cancers are located in a domain that is required for both the mirna processing function and transcriptional activity 45,48. Previously referred to as gain of function gof p53 proteins, we now term these oncomorphic mutations to better describe. By limiting the availability of primirnas or premirnas for processing, the. Find support for a specific problem on the support section of our website. Modulation of microrna processing by p53 semantic scholar.
Identification of new p53 target micrornas by bioinformatics. The p53dependent g1 arrest by clamidine is regulated by mirna16 given the observation that both the g1 arrest and increase in mirna16 by clamidine were p53dependent. Some viruses alter the functions of infected cells without killing them. Consistently, in response to stress conditions, both wt and mutant p53 accumulate in cells. This is a pdf file of an unedited manuscript that has been accepted for publication. The two founding members of the microrna family were originally identified in caenorhabditis elegans as genes that were required for the timed regulation of developmental events. However, the contribution of p53modulated mirnas during dna damage response is unclear. Current view of microrna processing shuai jiang, wei yan, 2016. Suzuki hi, yamagata k, sugimoto k, iwamoto t, kato s, miyazono k. Yang w, chendrimada tp, wang q, higuchi m, seeburg ph, shiekhattar r, nishikura k 2006 modulation of microrna processing and expression through rna editing by adar deaminases. The wellknown tumor suppressor p53 plays critical roles in the modulation of multiple cellular processes. Based on the findings from the online analysis website, mir8 targets p53 figure 6a.
A microrna abbreviated mirna is a small noncoding rna molecule containing about 22 nucleotides found in plants, animals and some viruses, that functions in rna silencing and posttranscriptional regulation of gene expression. An external file that holds a picture, illustration, etc. The wild type wt p53 protein transactivates genes and micrornas mirnas necessary in the response to cellular stress, which turn off growth and induce apoptosis. Similarly, the p53 tumor suppressor gene is the most frequently mutated gene in human cancer, and its loss or mutation leads to tumor formation in. Modulation of microrna processing by p53 hiroshi i. Downregulation of microrna8 improves immunologic function.
This gene is expressed in breast and other tissues, where it helps to repair damaged genomes and disrupts cells when the genome cannot be repaired shen et al. Possible role of tocopherols in the modulation of host. Asoke banerji phytochemistry, amrita school of biotechnology who is leading the efforts in the extraction and purification of natural products from various plant sources, we plan to test these compounds on the expression of gelatinases mmp2 and. The canonical mirna processing pathway consists of four. Our study reveals a previously unrecognized function of p53 in mirna processing, which may underlie key aspects of cancer biology. Utr with imperfect complementarity and function as translational repressors see below for a discussion of plant mirnas 4. Using highthroughput profiling, dysregulation of mirnas has been widely observed in different stages of cancer, and there is mounting evidence demonstrating. Oncomorphic tp53 mutations in gynecologic cancers lose the. Jul 23, 2009 these findings suggest that transcriptionindependent modulation of mirna biogenesis is intrinsically embedded in a tumour suppressive program governed by p53. Underlying mechanisms include the downregulation of histone acetyl transferases and consecutive activation of p53, but also the targeting of cyclin dependent kinases and their association partners. Modulation of microrna expression and function by adars. In principle, the processing of mir319 and mir159 precursors might lead to the accumulation of several mirnas. Pdf micrornas mirnas have emerged as key posttranscriptional regulators of gene expression, involved in diverse physiological and. Micrornas mirnas are pivotal regulators involved in various biological functions through the posttranscriptional regulation of gene expression.
Processing of plant microrna precursors briefings in. Nuclear receptors nrs are ligandactivated transcription factors that regulate gene transcription by binding to the promoter region or by interacting with other transcription factors. Modulation of pri mirna processing by other transcriptional regulators. Mutations in tp53 can alter the function of the p53 protein, and some mutations result in a mutated protein with oncogenic activity. A direct interaction between p53 and p68p72 facilitates p53 promoting of mirna processing. Disruption of p53 function is a fundamental event in the development of. Jpg, made by narayanese talk contribs after an illustration in esquelakerscher a, slack fj 2006. Viruses infect host cells releasing their genome dna or rna containing all information needed to replicate themselves. Considerable progress has been made in the past few years in understanding the transcription. Alternative processing of primary microrna transcripts by. These findings have prompted a great deal of investigation. Emerging paradigms of regulated microrna processing europe. Smad proteins bind a conserved rna sequence to promote microrna maturation by drosha. A large intergenic noncoding rna induced by p53 mediates global gene repression in the p53 response.
These mirnas are predicted to bind a large number of target mrnas. Widespread use of microrna arrays to profile microrna expression has indicated that the levels of many micrornas are altered during development and disease. This suggests that p53s ability to modulate mirna biogenesis could. In addition to direct transcriptional activation, wt p53 also acts through protein. Interaction of the oncogenic mir21 microrna and the p53. The study of the p53 gene transcriptional networks continues to raise particular interest in the field due to the increasing complexity of regulatory circuits and the functions of the extensive list of target genes spanning a myriad of different biological pathways. Second, tp53 is the epicenter of the mir422a genetic interaction network, exhibiting numerous direct and indirect connections with host restriction factors. Viswanathan sr, daley gq, gregory ri 2008 selective blockade of microrna processing by lin28. Considerable progress has been made in the past few years in understanding the transcription, biogenesis.
About about europe pmc funders joining europe pmc governance roadmap outreach. The ced is essential for drosha processing activity and is composed of a platform and a piwiargonautezwille paz. Increased exosomal microrna21 and microrna146a levels in the cervicovaginal lavage specimens of patients with cervical cancer previous article in journal an improved mlvf method and its comparison with traditional mlvf, spa typing, mlstscc mec and pfge for the typing of methicillinresistant staphylococcus aureus. Alterations of mirna expression and function contribute to both physiological and pathological processes such as development and cancer. The processing of plant precursors by multiple dcl1 cuts has been also observed in other cases 28, 82 and so far, is a distinctive feature not present in animal precursors.
Recent studies have demonstrated that mirnas interact with p53 and its. Microrna 21 mir21 is overexpressed virtually in all human cancers and displays oncogenic activity in a transgenic murine model. Our findings demonstrated another important aspect of this key tumor suppressor. Notably, mir612, which has the same seed sequence as mir1285, cannot bind to the 3. The role of vitamins and minerals in modulating the. Micrornas mirnas have emerged as key posttranscriptional regulators of gene expression, involved in diverse physiological and pathological processes.
Modulation of microrna and transcriptional regulation of. At least in animals, most mirnas bind to the target3. The viral genome takes control of the cells and helps the virus to evade the host immune system. Suzuki hi1, yamagata k, sugimoto k, iwamoto t, kato s, miyazono k. For several decades, p53 has been detected in cancer biopsies by virtue of its high protein expression level which is considered indicative of mutation. In mammalians, hif is a master regulator of hypoxia gene expression through direct binding to dna, while its role in microrna expression regulation, critical in the hypoxia response, is not elucidated genome wide. Taken together, these findings suggest an important role of p53 in the regulation of mirna expression, and at the same time, also suggest an important role of mirnas in mediating the role of p53 in tumor suppression as a new class of p53 target genes. Based on the findings from the online analysis website microrna. We also found that transcriptionally inactive p53 mutants interfere with a functional assembly between drosha complex and p68, leading to attenuation of mirna processing activity.
Drosha plays a critical role in the processing of primirna transcripts into. Modulation of microrna processing by p53 toru suzuki, hiroshi tamada department of cancer biology, graduate school of medicine, kyoto university, kyoto, japan this article has been withdrawn at the request of the editor. Microrna control of p53 juan liu, cen zhang, yuhan zhao, and zhaohui feng department of radiation oncology, rutgers cancer institute of new jersey, rutgers, state university of new jersey, new brunswick 08903, new jersey abstract tumor suppressor p53 plays a central role in tumor suppression. Cancers free fulltext atm dependent dusp6 modulation. The deletion of p53 promotes the development of liver fibrosis and tumor progression. Mutations in the tumor suppressor tp53 occur in almost all advanced ovarian cancers and in many advanced serous endometrial cancers. The publisher apologizes for any inconvenience this may cause. Acetylation of k120 is critical for the mirna processing activity of p53.
In some cases infected cells lose control over normal cell proliferation and becomes cancerous. Regulation of primary microrna processing creugny 2018. Interestingly, mirnas could act as either tumor suppressors or oncogenes depending on the functions of their targets. Pdf modulation of microrna processing by p53 researchgate. The p53 mutants suppressed the precursor and mature mirna levels of mir161, mir143 and mir206, in comparison with the constant level of primirnas, whereas wildtype p53 increased the pre. Identification and analysis of p53mediated competing. Disruption of p53 function is a fundamental event in the development of most cancers.
Thus, in the context of cotranscriptional mirna processing, mutant p53 may interfere with efficient association between primirnas and drosha and their cofactors in contrast to wildtype p53. Conclusion this study shows that mirnas could mediate the effects of oxaliplatin, and that p53 and tap73 could also partly regulate the role of mirnas in chemosensitivity. Brca1 forms a large multiprotein complex known as the brca1associated genome. Frontiers regulation of mutant p53 protein expression.
Analysis of microrna host gene expression correlation supports the idea that posttranscriptional mechanisms for microrna expression regulation are in action under hypoxia, and we provide evidence that hif can play a role by modulating the expression levels of microrna processing genes such as the downregulation of dicer. Finally the repression of mirna processing by the partial depletion of. This is a pdf file of an unedited manuscript that has been. Modulation of microrna processing by mismatch repair. Davis bn, hilyard ac, lagna g, hata a 2008 smad proteins control droshamediated microrna maturation.
1239 228 341 1364 876 1019 1469 152 253 869 389 419 1584 51 716 585 473 664 543 1466 760 1390 636 576 577 438 1139 446