Further experiments indicated that mir29b inhibited endometrial fibrosis via. Sp1 enhances its own expression by participating in a nfkappabhdac complex that further represses mir 29b transcription. Microrna7 targets igf1r insulinlike growth factor 1 receptor in tongue squamous cell carcinoma cells. The x sign over the red boxes indicates the mir 29b sites that were deleted.
Microrna29b inhibits peritoneal fibrosis in a mouse model. These results indicated that dnmt3b was a direct target of mir 29b in tscc cell lines. Role for mir29b suppression in multiple myeloma klinge. Results suggest that mir 29b negatively regulates dna methyltransferase 1 dnmt1 expression by targeting sp1 in t cells. Expression of the transcription factor sp1 and its regulatory hsamir29b in peripheral blood mononuclear cells from patients with alzheimers disease. Micrornas modulate male fertility by regulating gene expression. The specific role for mir 29b 3p in melanoma has not been well studied. Inverse correlation between ezh2 and mir 29b in mm patientderived plasma cells. Overexpression of mir 29b contributes to reduction of dnmt1 levels and dna hypomethylation in systemic lupus erythematosus. Microrna29b inhibits endometrial fibrosis by regulating. Microrna29b attenuates nonsmall cell lung cancer metastasis. Mar 03, 2015 the role of mir 29b in cancer cell metastasis and invasion. A novel therapeutic strategy in acute myeloid leukemia.
Bhdac mir 29b regulatory network in kitdriven myeloid leukemia. Microrna29b regulates ethanolinduced neuronal apoptosis in. It is known that within the mir 29 family, mir 29a is coexpressed with mir 29b 1 and mir. Here, we find that mir 29b could promote radiosensitivity in radioresistant subpopulations of cervical cancer cells. Micrornas may therefore be part of the upstream drivers of the global gene expression modulation correlated with aging and agingrelated.
Here we show that mir 29b promotes skeletal muscle. Stat3, yy1, and jun inhibit and sp1 stimulates mir 29b 1 transcription 11. To elucidate how dnmt1 regulates the kit gene, we focused on the sp1 mir29b network, because sp1 mir29b has been shown to regulate kit transcription in leukemia, 31 and mir29b was silenced in. B changes in mir29b expression and kit protein levels in kasumi1 cells transfected with mir29b or antagomir29b amir29b for 72 hr. Upregulated sp1 then binds nfkappab and transactivates kit. In conclusion, we demonstrated that mir 29b was reduced in tscc and acted as a tumor suppressor at lest partly by targeting sp1. Mir29b plays an important role in ethanol neurotoxicity in the developing cerebellum. Microrna 29b inhibits endometrial fibrosis by regulating the sp1 tgf. Sp1 mediates microrna29cregulated type i collagen production in renal tubular epithelial cells. Results revealed that miat overexpression significantly decreased the expression of mir29b figure 6b, but increased the expression of sp1 figure 6c. Long noncoding rna miat acts as a biomarker in diabetic.
Ten human nonsmall cell lung cancer nsclc cell lines and samples from thirty patients with nsclc were analyzed for the expression of mir 29b by quantitative rtpcr. Immunoliposomal delivery of mir29b by targeting tumor. Micrornas emerged as fine regulators of gene expression in many biological contexts and they are modulated by age. Expression of the transcription factor sp1 and its regulatory hsa mir 29b in peripheral blood mononuclear cells from patients with alzheimers disease. Bioinformatic tools were employed to ascertain genes of interest of the sperm mirnas. A number of micrornas mirnas, mirs have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. To elucidate how dnmt1 regulates the kit gene, we focused on the sp1 mir 29b network, because sp1 mir 29b has been shown to regulate kit transcription in leukemia, 31 and mir 29b was silenced in. Microsoft download manager is free and available for download now. Delay of agomir29b treatment until endometrial fibrosis was established on day 4 also halted the progression of disease. According to these results, sp1 and its regulatory hsa mir 29b are deregulated in ad patients, possibly leading to aberrant production of downstream target genes involved in the pathogenesis. Bdriven renal inflammation in the diabetic kidney of dbdb mice.
Mir29b suppresses proliferation, migration, and invasion of tongue squamous cell carcinoma through ptenakt signaling pathway by targeting sp1. Mir29bsp1fut4 axis modulates the malignancy of leukemia. Here, we show that kit mutations lead to mycdependent mir 29b repression and increased levels of the mir 29b target sp1 in kitdriven leukemia. The microsoft download manager solves these potential problems. Suppression of type i collagen expression by mir29b via pi3k. Microrna29b regulates ethanolinduced neuronal apoptosis. Download scientific diagram mir29b activated the ptenakt signaling pathway by reducing the expression of sp1. Mar 29, 2020 results suggest that mir29b negatively regulates dna methyltransferase 1 dnmt1 expression by targeting sp1 in t cells. We experimentally validated the predicted mir 29b 3p regulation of lamc1 and ppic and lasp1, and show that dysregulation of mir 29b 3p or these mrna targets can influence cellular invasiveness in vitro. Chiling chiang, frank w frissora, zhiliang xie, xiaomeng huang, rajeswaran mani, sivasubramanian baskar, christoph rader, kenneth k.
Human mir 102 is a homologue of mouse mir 29b and so has been renamed here for consistency. Microrna29b contributes to collagens imbalance in human. Loss of microrna cluster mir29ab1 in sporadic alzheimer. Mir 29b regulates ethanolinduced apoptosis of cerebellar granule neurons in the developing cerebellum via sp1 raxpkr cascade. Therapeutic delivery of mir29b enhances radiosensitivity in. These results indicate that the lncrna malat1 transcriptionally inhibits mir 29b expression by modulating the amount of h3k27me3 of its promoter. B dna binding as confirmed by antibody supershift figure s4c, thereby closing the mir29b sp1 autoregulatory loop. Higher mir29b pretreatment expression is associated with improved response to decitabine and better outcome in aml. Reporter assays showed that mir29b targeted col2a1 and col1a2 3. Some key transcriptional upregulators of mir 29 family members include sp1, runx3, and cebpa 2729. Bzb cells triggered downregulation of validated mir29b targets, such as sp1, cdk6, and to a lesser extent mcl1 figure 2d, indicating that ezh2depletion induced a functionally active mir29b.
Overexpression of mir29b contributes to reduction of dnmt1 levels and dna hypomethylation in systemic lupus erythematosus. Immunoliposomal delivery of mir 29b by targeting tumor antigen ror1 induces epigenetic reprograming in humanror1expressed mouse model of chronic lymphocytic leukemia. Yet, this mir 29b downregulation of dna methyltransferase was indirect by targeting sp1, a transactivator of the dnmt1 gene garzon et al. Mir29b suppresses proliferation, migration, and invasion. Clinically, sp1 and fut4 were upregulated and positively correlated with poor overall survival of aml patients. A schematic diagram illustrating mir29 regulation of col7a1. Apr, 2010 a sp1 mir29b expression ratio measured by microarray in bone marrow samples from cancer and leukemia group b runx1runx1t1positive patients with cytogenetically normal aml and kit mut or kit wt.
Consistent with these results, these patients have high sp1mir29b ratio figure 4a. Mir 29b gene transfer prevents peritoneal fibrosis in a mouse model of peritoneal dialysis. Jun 16, 2016 the antiapoptosis effect and downregulated sp1 expression effect of rsv was prevented by mir29b inhibitor p sp1 pathway play roles in the anti. Utr with the localization of the 4 predicted premir29b binding sites. Hickey, jianhua yu, heiko becker, kati maharry, michael d. In conclusion, mir29b may play a protective role in diabetic kidney disease and may have. Loss of sp1 protein in turn downregulates dnmt1 expression. Here we show a comparable function for mir 29b in osteogenic differentiation of human somatic stem cells confirming human ctnnbip1 and hdac4 as mir 29b targets in our hek293tcell based validation assay. Mir29b may be a new preventivetherapeutic target for fetal alcohol spectrum disorders. Nov 09, 2016 the microsoft download manager solves these potential problems.
Abstract 3960overwhelming osteoclast ocl activation plays a central role in multiple myeloma mmrelated bone disease. However, the reported studies on mir 29b 3pregulated breast cancer are limited so far. Targeted delivery of microrna29b by transferrinconjugated. Results revealed that miat overexpression significantly decreased the expression of mir 29b figure 6b, but increased the expression of sp1 figure 6c. In addition, mir29b3p, one mir29 family member, can regulate cardiac fibrosis by modulating collagen type i alpha 1 col1a1 either directly or indirectly through sp1, since sp1 can also regulate the expression of col4a1. Mir29b antagonizes the proinflammatory tumorpromoting. A widespread modulation of gene expression occurs in the aging brain, but little is known as to the upstream drivers of these changes. Cancer metastasis is a multistage process that includes extracellular matrix remodeling, blood vessel recruitment, tumor cell entry and exit from circulation, and survival in distant organs. In order to verify it, admiat was constructed and transfected to rmc1 cells and the expression of mir 29b and its downstream gene sp1 was detected. Overexpression of mir29b before injury prevented endometrial fibrosis including collagen accumulation and epithelialmesenchymal transition. Microrna29b induces global dna hypomethylation and tumor.
It should be pointed out that although mir29b is reported to be able to target sp1 in mononuclear cells and tbox in t cells,24,25,40 and both mrna and protein levels of sp1 and tbet in the diabetic kidney in this study were found to be tightly associated with the expression of mir29b, the direct regulatory mechanisms of mir29b on sp1 and t. The mir 29 microrna precursor, or premirna, is a small rna molecule in the shape of a stemloop or hairpin. Select sequences and output type, then click fetch sequences. Experiments were conducted in conditionally immortalized human podocytes.
Overexpression of mir29b inhibited the pi3kaktsp1 pathway, and attenuated the expression of col1a1. Jan 01, 20 read expression of the transcription factor sp1 and its regulatory hsamir29b in peripheral blood mononuclear cells from patients with alzheimers disease, journal of alzheimers disease on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Mechanistic studies showed that bortezomib upregulates mir29b and then epigenetically downregulates flt3. Mir 29b antagonizes the proinflammatory tumorpromoting activity of multiple myelomaeducated dendritic cells. Although the role of app and psen genes in genetic alzheimers disease ad cases is well established, fairly little is known about the molecular mechanisms affecting a. Strong antifibrotic effects of mir 29 family have been confirmed in liver, kidney, and other organs.
Pdf targeted delivery of microrna 29b by transferrin. An expression analysis of sp1 and its regulatory micrornas hsa mir 29b and hsa mir 375 was performed in peripheral blood mononuclear cells pbmcs, together with sp1. Moreover, sp1 rs176951056 t allele is likely a protective factor in the male population. Bhdac complexes thereby resulting in mir 29b upregulation, sp1 downregulation and inhibition of the kit gene transactivation. Initial reports suggested that mir 29b 1 preferentially localizes to the nucleus 8,9, but more recent singlemolecule fluorescencebased analysis revealed that although mir 29b localizes. Therapeutic delivery of mir 29b enhances radiosensitivity. Previous studies showed that sp1 upregulated mgmt table 1. Mir 29b plays an important role in ethanol neurotoxicity in the developing cerebellum. Higher mir 29b pretreatment expression is associated with improved response to decitabine and better outcome in aml. Sp1 is a negative regulator of mir29b expression in multiple myeloma cells. We also found that mir 29b sp1 ptenakt axis regulated the proliferation, cycle, apoptosis, migration, and invasion of tscc cells. As a tumor suppressor, mir29 restrains cancer progression by promoting. There are two chromosomal locations of mir 29b in the human genome. Shujun liu, lai chu wu, jiuxia pang, ramasamy santhanam, sebastian schwind, yue zhong wu, christopher j.
The roles of microrna families in hepatic fibrosis cell. Thus, designing a strategy to increase mir 29b levels in aml blasts may be of therapeutic value. B dna binding as confirmed by antibody supershift figure s4c, thereby closing the mir 29b sp1 autoregulatory loop. Each arm of the hairpin can be processed into one member of a closely related family of short noncoding rnas that are involved in regulating gene expression. Apr 28, 2017 in order to verify it, admiat was constructed and transfected to rmc1 cells and the expression of mir29b and its downstream gene sp1 was detected.
Mir 29b sp1 fut4 crosstalk regulates cd44 fucosylation and activates wnt. Nov 26, 2012 ar42 downregulates the mir29b targets dnmt1, dnmt3a, dnmt3b and sp1. B changes in mir 29b expression and kit protein levels in kasumi1 cells transfected with mir 29b or antagomir 29b a mir 29b for 72 hr. Mir 29b sp1 fut4 axis modulates the malignancy of leukemia. Microrna29b inhibits endometrial fibrosis by regulating the. The intended in vivo target for this compound was the sp1 nf. Overexpression of mir 29b before injury prevented endometrial fibrosis including collagen accumulation and epithelialmesenchymal transition. It is known that mir29b downregulates dnmt3a, dnmt3b and sp1 directly, and reduces expression of dnmt1 indirectly by. The mir29 family members regulate the progress of hepatic fibrosis by following ways. Sp1nfkappabhdacmir29b regulatory network in kitdriven.
The active mir 29b binds dnmt3a, 3b, and sp1 mrna either blocking translation or targeting them for degradation. Ctnnbip1 was also regulated by mir 10a and cdk6 was targeted by mir 22, mir 26a, mir 26b and mir 29b. Mechanistic studies showed that bortezomib upregulates mir 29b and then epigenetically downregulates flt3. Notably, therapeutic delivery of mir 29b mimics via r11sspei nanoparticle, whose specificity has been proved by our previous studies, can sensitize the tumor to radiation in a xenograft model. Our data indeed indicated that bortezomib disrupts both sp1 nf. Targeted delivery of microrna 29b by transferrinconjugated anionic lipopolyplex nanoparticles. They further revealed that bortezomib can upregulate mir 29b and increase the clinical sensitivity of tumors to decitabine. In this study, sp1 was also validated as a new mir7a target in cardiomyocytes through luciferase assays and gainof. Nov 21, 2017 mir29b antagonizes the proinflammatory tumorpromoting activity of multiple myelomaeducated dendritic cells. Notably, therapeutic delivery of mir 29b mimics via r11sspei nanoparticle, whose specificity has been proved by our previous studies, can sensitize the tumor to. Apr, 2010 notably, ectopic mir29b expression disrupted sp1 binding to the mir29b enhancer region figure 5e through abrogation of sp1 protein and disruption of sp1 nf. Herein, we investigated the role and mechanism of mir 29b 3p in the triple negative breast cancer cell line mdamb231. Subsequent genome assemblies suggest the presence of only one mir 102 locus on chromosome 7.
Microrna 29b inhibits diabetic nephropathy in dbdb mice. In the current study, we showed that enforced expression of mir29b in acute myeloid leukemia cells resulted in marked reduction of the. A study in bacteriainduced gastric cancers highlighted the involvement of three mirnas mir 124a1, mir 124a2, and mir 124a3. Moreover, mir 29b directly affected the binding of sp1 and fut4 promoter region, which further mediated lscs proliferation, apoptosis and drugresistance through fucosylatedcd44 via activation of wnt. Immediately below there is a schema of the luciferase reporter assays used in the luciferase experiments. The relative mir 29b 3p expression in different breast cancer cell lines were determined by qrtpcr. The circular rna cdr1as promotes myocardial infarction by. Research paper inhibition of ezh2 triggers the tumor. Resveratrol inhibits diabeticinduced muller cells apoptosis. In fact, silencing of hdac4 by shrnas inhibited multiple myeloma cell survival and migration and triggered apoptosis and autophagy, along with the induction of mir29b expression by promoter hyperacetylation, leading to the downregulation of prosurvival mir29b targets sp1, mcl1. Mir29bsp1fut4 axis modulates the malignancy of leukemia stem. Analysis of the correlation between expression of mir29a, mir29b and mir29c in primary glioma and its clinicopathological parameters cases mir29a mir29b mir29c. Expression of the transcription factor sp1 and its regulatory hsamir29b in peripheral blood mononuclear cells. Jun 11, 2015 our pilot study using mirna pcr array found that mirna 29b mir 29b is differentially expressed in primary cultured cd3positive a549 cells compared with cd3negative a549 cells.
Mir29b sp1 fut4 crosstalk regulates cd44 fucosylation and activates wnt. Expression of the transcription factor sp1 and its regulatory. They further revealed that bortezomib can upregulate mir29b and increase the clinical sensitivity of tumors to decitabine. Expression of the transcription factor sp1 and its regulatory hsamir. Mature mir 29 family members target proteins that are. Pathway analysis indicated that a number of these genes are positively regulated by the transcription factor sp1, which is a validated target of mir29b, suggesting that inhibition of sp1 by mir29 may be an important factor in the overall effects on gene expression mediated by mir29b. Mir29b regulates ethanolinduced apoptosis of cerebellar granule neurons in the developing cerebellum via sp1 raxpkr cascade. The relative mir 29b 3p expression in different breast. Utr with the localization of the 4 predicted pre mir 29b binding sites. Notably, ectopic mir 29b expression disrupted sp1 binding to the mir 29b enhancer region figure 5e through abrogation of sp1 protein and disruption of sp1 nf.
The x sign over the red boxes indicates the mir29b sites that were deleted. A sp1 mir 29b expression ratio measured by microarray in bone marrow samples from cancer and leukemia group b runx1runx1t1positive patients with cytogenetically normal aml and kit mut or kit wt. The authors of this report 7 did not distinguish whether both chromosomal locations were the source of mir 29b in dcs, or if one locus was active, nor did they examine the expression of mir 29a or mir. Bhdac complexes thereby resulting in mir 29b upregulation, sp1 downregulation and. Therapeutic targeting of mir29bhdac4 epigenetic loop in. Then downregulated flt3 leads to conspicuous downregulation of sp1 and destroys the sp1 nf. Sp1 is a negative regulator of mir 29b expression in multiple myeloma cells. Expression of the transcription factor sp1 and its. It also allows you to suspend active downloads and resume downloads that have failed. Microrna29b inhibits diabetic nephropathy in dbdb mice. Thus, designing a strategy to increase mir29b levels in aml blasts may be of therapeutic value. Download microsoft identity manager 2016 service pack 1. Mir 29b may be a new preventivetherapeutic target for fetal alcohol spectrum disorders.