Genomes and Genes
Gene Symbol: MIR34A
Description: microRNA 34a
Alias: MIRN34A, miRNA34A, mir-34
- Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, et al. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS ONE. 2012;7:e33778 pubmed publisher..In the present study, the effects of miR-34a on osteosarcoma and the possible mechanism by which miR-34a affected the tumor growth and metastasis of osteosarcoma were investigated...
- Vinall R, Ripoll A, Wang S, Pan C, deVere White R. MiR-34a chemosensitizes bladder cancer cells to cisplatin treatment regardless of p53-Rb pathway status. Int J Cancer. 2012;130:2526-38 pubmed publisher..The combined data indicate that elevation of miR-34a expression levels before chemotherapy would be of benefit to MI-TCC patients, particularly in a setting of low miR-34a expression. ..
- Li W, Ma M, Dong L, Wang F, Chen L, Li X. MicroRNA-34a targets notch1 and inhibits cell proliferation in glioblastoma multiforme. Cancer Biol Ther. 2011;12:477-83 pubmed publisher..Knockdown of notch1 showed similar cellular functions as overexpression of miR-34a both in vitro and in vivo. Collectively, our findings show that miR-34a is downregulated in GBM cells and inhibits GBM growth by targeting notch1. ..
- De Antonellis P, Medaglia C, Cusanelli E, Andolfo I, Liguori L, De Vita G, et al. MiR-34a targeting of Notch ligand delta-like 1 impairs CD15+/CD133+ tumor-propagating cells and supports neural differentiation in medulloblastoma. PLoS ONE. 2011;6:e24584 pubmed publisher..Thus, this technology forms the basis for their therapeutic use for the delivery of miR-34a in brain-tumor treatment, with no signs of toxicity described to date in non-human primate trials. ..
- Chen Q, Yu L, Tsang P, Wei J, Song Y, Cheuk A, et al. Systematic proteome analysis identifies transcription factor YY1 as a direct target of miR-34a. J Proteome Res. 2011;10:479-87 pubmed publisher..YY1 is a negative regulator of p53, and it plays an essential role in cancer biology. Therefore, YY1 is another important direct target of miR-34a which closely regulates TP53 activities. ..
- Zenz T, Mohr J, Eldering E, Kater A, Bühler A, Kienle D, et al. miR-34a as part of the resistance network in chronic lymphocytic leukemia. Blood. 2009;113:3801-8 pubmed publisher..The elucidation of mechanisms underlying miR-34a regulation and overcoming its role in chemotherapy resistance warrant further study. ..
- Mudduluru G, Ceppi P, Kumarswamy R, Scagliotti G, Papotti M, Allgayer H. Regulation of Axl receptor tyrosine kinase expression by miR-34a and miR-199a/b in solid cancer. Oncogene. 2011;30:2888-99 pubmed publisher..These results indicate that Axl receptor expression can be regulated by miR-34a and miR-199a/b, which are suppressed by promoter methylation in solid cancer cells. ..
- Kumamoto K, Spillare E, Fujita K, Horikawa I, Yamashita T, Appella E, et al. Nutlin-3a activates p53 to both down-regulate inhibitor of growth 2 and up-regulate mir-34a, mir-34b, and mir-34c expression, and induce senescence. Cancer Res. 2008;68:3193-203 pubmed publisher..together, we conclude that nutlin-3a induces senescence through p53 activation in normal human fibroblasts, and p53-mediated mir34a, mir34b, and mir34c up-regulation and ING2 down-regulation may be involved in the senescence pathway.
- Dang Y, Luo D, Rong M, Chen G. Underexpression of miR-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET. PLoS ONE. 2013;8:e61054 pubmed publisher..In conclusion, miR-34a may act as a tumor suppressor miRNA of HCC. The strategies to increase miR-34a level might be a critical targeted therapy for HCC in future. ..
- Jamieson N, Morran D, Morton J, Ali A, Dickson E, Carter C, et al. MicroRNA molecular profiles associated with diagnosis, clinicopathologic criteria, and overall survival in patients with resectable pancreatic ductal adenocarcinoma. Clin Cancer Res. 2012;18:534-45 pubmed publisher..miRNA expression profiles correlated with overall survival of PDAC following resection, indicating that miRNAs provide prognostic utility. ..
- Welch C, Chen Y, Stallings R. MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cells. Oncogene. 2007;26:5017-22 pubmed..Thus, adding to the increasing role of miRNAs in cancer, miR-34a may act as a suppressor of NB tumorgenesis. ..
- Tanaka N, Toyooka S, Soh J, Tsukuda K, Shien K, Furukawa M, et al. Downregulation of microRNA-34 induces cell proliferation and invasion of human mesothelial cells. Oncol Rep. 2013;29:2169-74 pubmed publisher..The present study, together with the results of our previous report, strongly suggest that miR-34s play an important role in the early carcinogenic process involved in the transformation of human mesothelial cells to MM. ..
- Ghawanmeh T, Thunberg U, Castro J, Murray F, Laytragoon Lewin N. miR-34a expression, cell cycle arrest and cell death of malignant mesothelioma cells upon treatment with radiation, docetaxel or combination treatment. Oncology. 2011;81:330-5 pubmed publisher..Microtubule formation and other related functions by docetaxel might be the most suitable treatment modulation in both sarcomatoid and epithelial types of MM. ..
- Dutta K, Zhong Y, Liu Y, Yamada T, Akatsuka S, Hu Q, et al. Association of microRNA-34a overexpression with proliferation is cell type-dependent. Cancer Sci. 2007;98:1845-52 pubmed
- Bandi N, Vassella E. miR-34a and miR-15a/16 are co-regulated in non-small cell lung cancer and control cell cycle progression in a synergistic and Rb-dependent manner. Mol Cancer. 2011;10:55 pubmed publisher..Since miR-34a and miR-15a/16 are frequently down-regulated in the same tumour tissue, administrating a combination of both miRNAs may also potentiate their therapeutic impact. ..
- Du R, Sun W, Xia L, Zhao A, Yu Y, Zhao L, et al. Hypoxia-induced down-regulation of microRNA-34a promotes EMT by targeting the Notch signaling pathway in tubular epithelial cells. PLoS ONE. 2012;7:e30771 pubmed publisher..Our study provides evidence that the hypoxia-induced decrease of miR-34a expression could promote EMT in renal tubular epithelial cells by directly targeting Notch1 and Jagged1, and subsequently, Notch downstream signaling. ..
- Mandke P, Wyatt N, Fraser J, Bates B, Berberich S, Markey M. MicroRNA-34a modulates MDM4 expression via a target site in the open reading frame. PLoS ONE. 2012;7:e42034 pubmed publisher..These data establish a mechanism for the observed DNA damage-induced negative regulation of MDM4 and potentially provide a novel means to manipulate MDM4 expression without introducing DNA damage. ..
- Xia J, Duan Q, Ahmad A, Bao B, Banerjee S, Shi Y, et al. Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells. Curr Drug Targets. 2012;13:1750-6 pubmed..Our findings suggest that genistein could function as a non-toxic activator of a miRNA that can suppress the proliferation of PC cells. ..
- Chen F, Hu S. Effect of microRNA-34a in cell cycle, differentiation, and apoptosis: a review. J Biochem Mol Toxicol. 2012;26:79-86 pubmed publisher..Ectopic miR-34a expression induces apoptosis, cell cycle arrest, and differentiation or reduces migration. This review summarizes the progress regarding the role of miR-34a in cell cycle, differentiation, and apoptosis. ..
- Nakatani F, Ferracin M, Manara M, Ventura S, Del Monaco V, Ferrari S, et al. miR-34a predicts survival of Ewing's sarcoma patients and directly influences cell chemo-sensitivity and malignancy. J Pathol. 2012;226:796-805 pubmed publisher..High expression of miR34a can be detected also in paraffin-embedded tissues by in situ hybridization, thus contributing to an easy routine ..
- Yamamura S, Saini S, Majid S, Hirata H, Ueno K, Chang I, et al. MicroRNA-34a suppresses malignant transformation by targeting c-Myc transcriptional complexes in human renal cell carcinoma. Carcinogenesis. 2012;33:294-300 pubmed publisher..Our results demonstrate that miR-34a suppresses assembly and function of the c-Myc complex that activates or elongates transcription, indicating a novel role of miR-34a in the regulation of transcription by c-Myc. ..
- Pang R, Leung C, Ye T, Liu W, Chiu P, Lam K, et al. MicroRNA-34a suppresses invasion through downregulation of Notch1 and Jagged1 in cervical carcinoma and choriocarcinoma cells. Carcinogenesis. 2010;31:1037-44 pubmed publisher..Our results provide evidence that miR-34a inhibits invasiveness through regulation of the Notch pathway and its downstream matrix degrading enzyme. ..
- Kim N, Kim H, Li X, Lee I, Choi H, Kang S, et al. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol. 2011;195:417-33 pubmed publisher..These results identify a new link between p53, miR-34, and Snail1 in the regulation of cancer cell EMT programs. ..
- Castro R, Ferreira D, Afonso M, Borralho P, Machado M, Cortez Pinto H, et al. miR-34a/SIRT1/p53 is suppressed by ursodeoxycholic acid in the rat liver and activated by disease severity in human non-alcoholic fatty liver disease. J Hepatol. 2013;58:119-25 pubmed publisher..Potential endogenous modulators of NAFLD pathogenesis may ultimately provide new tools for therapeutic intervention. ..
- Craig V, Cogliatti S, Imig J, Renner C, Neuenschwander S, Rehrauer H, et al. Myc-mediated repression of microRNA-34a promotes high-grade transformation of B-cell lymphoma by dysregulation of FoxP1. Blood. 2011;117:6227-36 pubmed publisher..In conclusion, our results elucidate a novel Myc- and FoxP1-dependent pathway of malignant transformation and suggest miR-34a replacement therapy as a promising strategy in lymphoma treatment. ..
- Ji Q, Hao X, Zhang M, Tang W, Yang M, Li L, et al. MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS ONE. 2009;4:e6816 pubmed publisher..Restoration of miR-34 may hold significant promise as a novel molecular therapy for human pancreatic cancer with loss of p53-miR34, potentially via inhibiting pancreatic cancer stem cells. ..
- Zhao G, Guo J, Li D, Jia C, Yin W, Sun R, et al. MicroRNA-34a suppresses cell proliferation by targeting LMTK3 in human breast cancer mcf-7 cell line. DNA Cell Biol. 2013;32:699-707 pubmed publisher..Taken together, these results suggest that miR-34a inhibits breast cancer proliferation by targeting LMTK3 and might be used as an anti-ER? agent in breast cancer therapy. ..
- Siemens H, Jackstadt R, Hünten S, Kaller M, Menssen A, Götz U, et al. miR-34 and SNAIL form a double-negative feedback loop to regulate epithelial-mesenchymal transitions. Cell Cycle. 2011;10:4256-71 pubmed publisher..In conclusion, the frequent inactivation of p53 and/or miR-34a/b/c found in cancer may shift the equilibrium of these reciprocal regulations towards the mesenchymal state and thereby lock cells in a metastatic state. ..
- Hashimi S, Fulcher J, Chang M, Gov L, Wang S, Lee B. MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation. Blood. 2009;114:404-14 pubmed publisher..Thus, our novel approach identified and validated some miRNA-protein networks involved in phenotypic and functional MDDC differentiation. ..
- Yamakuchi M, Ferlito M, Lowenstein C. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci U S A. 2008;105:13421-6 pubmed publisher..Finally, miR-34a itself is a transcriptional target of p53, suggesting a positive feedback loop between p53 and miR-34a. Thus, miR-34a functions as a tumor suppressor, in part, through a SIRT1-p53 pathway. ..
- Weeraratne S, Amani V, Neiss A, Teider N, Scott D, Pomeroy S, et al. miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol. 2011;13:165-75 pubmed publisher..Our work establishes a role for miR-34a in modulating responsiveness to chemotherapy in medulloblastoma and presents a novel positive feedback mechanism involving miR-34a and p53, via direct targeting of MAGE-A. ..
- Lal A, Thomas M, Altschuler G, Navarro F, O Day E, Li X, et al. Capture of microRNA-bound mRNAs identifies the tumor suppressor miR-34a as a regulator of growth factor signaling. PLoS Genet. 2011;7:e1002363 pubmed publisher..Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division. ..
- Zhao J, Lammers P, Torrance C, Bader A. TP53-independent function of miR-34a via HDAC1 and p21(CIP1/WAF1.). Mol Ther. 2013;21:1678-86 pubmed publisher..The data suggest that miR-34 controls a tumor suppressor pathway previously reserved for TP53 and provides an attractive therapeutic strategy for cancer patients irrespective of TP53 status. ..
- Li N, Fu H, Tie Y, Hu Z, Kong W, Wu Y, et al. miR-34a inhibits migration and invasion by down-regulation of c-Met expression in human hepatocellular carcinoma cells. Cancer Lett. 2009;275:44-53 pubmed publisher..Taken together, these results provide evidence to show the suppression role of miR-34a in tumor migration and invasion through modulation of the c-Met signaling pathway. ..
- Lu X, Chen Z, Liang H, Li Z, Zou X, Luo H, et al. Thyroid hormone inhibits TGF?1 induced renal tubular epithelial to mesenchymal transition by increasing miR34a expression. Cell Signal. 2013;25:1949-54 pubmed publisher..Meanwhile, T3 induced the expression of miR34a. Molecularly, the T3 receptor could directly bind the T3R recognition motif at the -1505 to -1526bp and -604 to -..
- Wu J, Wu G, Lv L, Ren Y, Zhang X, Xue Y, et al. MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1. Carcinogenesis. 2012;33:519-28 pubmed publisher..However, in vivo data indicate that the p53-miR-34a pathway is not the major regulator of Fra-1 expression in human colon cancer tissues. ..
- Akao Y, Noguchi S, Iio A, Kojima K, Takagi T, Naoe T. Dysregulation of microRNA-34a expression causes drug-resistance to 5-FU in human colon cancer DLD-1 cells. Cancer Lett. 2011;300:197-204 pubmed publisher..These findings suggest that miR-34a targeting the Sirt1 and E2F3 genes could negatively regulate, at least in part, the resistance to 5-FU in human colorectal cancer DLD-1 cells. ..
- Luan S, Sun L, Huang F. MicroRNA-34a: a novel tumor suppressor in p53-mutant glioma cell line U251. Arch Med Res. 2010;41:67-74 pubmed publisher..Our results demonstrate that miR-34a acts as a tumor suppressor in p53-mutant glioma cells U251, partially through regulating SIRT1. ..
- Zhao H, Ma B, Wang Y, Han T, Zheng L, Sun C, et al. miR-34a inhibits the metastasis of osteosarcoma cells by repressing the expression of CD44. Oncol Rep. 2013;29:1027-36 pubmed publisher..Therefore, it can be concluded that through the inhibition of CD44 expression levels, miR-34a plays a significant role in the migration and invasion of osteosarcoma cells...
- Cao W, Yang W, Fan R, Li H, Jiang J, Geng M, et al. miR-34a regulates cisplatin-induce gastric cancer cell death by modulating PI3K/AKT/survivin pathway. Tumour Biol. 2014;35:1287-95 pubmed publisher..miR-34a over-expression could improve the sensitivity of gastric cancer cells against cisplatin-based chemotherapies, with PI3K/AKT/survivin signaling pathway possibly involved in the mechanism. ..
- Cole K, Attiyeh E, Mosse Y, Laquaglia M, Diskin S, Brodeur G, et al. A functional screen identifies miR-34a as a candidate neuroblastoma tumor suppressor gene. Mol Cancer Res. 2008;6:735-42 pubmed publisher..BCL2 and MYCN were identified as miR-34a targets and likely mediators of the tumor suppressor phenotypic effect. These data support miR-34a as a tumor suppressor gene in human neuroblastoma. ..
- Lodygin D, Tarasov V, Epanchintsev A, Berking C, Knyazeva T, Körner H, et al. Inactivation of miR-34a by aberrant CpG methylation in multiple types of cancer. Cell Cycle. 2008;7:2591-600 pubmed..These results show that miR-34a represents a tumor suppressor gene which is inactivated by CpG methylation and subsequent transcriptional silencing in a broad range of tumors. ..
- Ji Q, Hao X, Meng Y, Zhang M, Desano J, Fan D, et al. Restoration of tumor suppressor miR-34 inhibits human p53-mutant gastric cancer tumorspheres. BMC Cancer. 2008;8:266 pubmed publisher..Our study suggests that restoration of the tumor suppressor miR-34 may provide a novel molecular therapy for p53-mutant gastric cancer. ..
- Wei J, Song Y, Durinck S, Chen Q, Cheuk A, Tsang P, et al. The MYCN oncogene is a direct target of miR-34a. Oncogene. 2008;27:5204-13 pubmed publisher..This study demonstrates one important regulatory role of miR-34a in cell growth and MYCN suppression in neuroblastoma. ..
- Kim N, Kim H, Kim N, Lee I, Choi H, Li X, et al. p53 and microRNA-34 are suppressors of canonical Wnt signaling. Sci Signal. 2011;4:ra71 pubmed publisher..These data provide insight into the mechanisms by which a p53-miR-34 network restrains canonical Wnt signaling cascades in developing organisms and human cancer. ..
- Li B, Hu Y, Ye F, Li Y, Lv W, Xie X. Reduced miR-34a expression in normal cervical tissues and cervical lesions with high-risk human papillomavirus infection. Int J Gynecol Cancer. 2010;20:597-604 pubmed publisher..The inhibition of miR-34a expression induced by HR-HPV E6 in the p53-dependent pathway is probably an early-onset event in the development of cervical cancer. ..
- Sun F, Fu H, Liu Q, Tie Y, Zhu J, Xing R, et al. Downregulation of CCND1 and CDK6 by miR-34a induces cell cycle arrest. FEBS Lett. 2008;582:1564-8 pubmed publisher..Taken together, our data suggest that the effects of miR-34a on G1 cell cycle arrest are through the down-regulation of CCND1 and CDK6, which is associated with other targets of miR-34a either additively or synergistically. ..
- Dufour A, Palermo G, Zellmeier E, Mellert G, Duchateau Nguyen G, Schneider S, et al. Inactivation of TP53 correlates with disease progression and low miR-34a expression in previously treated chronic lymphocytic leukemia patients. Blood. 2013;121:3650-7 pubmed publisher..In addition, only a complete loss of TP53 function correlated with low microRNA-34a expression levels. This trial was registered at www.clinicaltrials.gov as #NCT00090051. ..
- Wang W, Li T, Han G, Li Y, Shi L, Li H. Expression and role of miR-34a in bladder cancer. Indian J Biochem Biophys. 2013;50:87-92 pubmed..These findings suggest that the relative low expression of miRNA-34a might be involved in the tumorigenesis of bladder cancer. ..
- Kumar B, Yadav A, LANG J, Teknos T, Kumar P. Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS ONE. 2012;7:e37601 pubmed publisher..Taken together, these findings suggest that dysregulation of miR-34a expression is common in HNSCC and modulation of miR34a activity might represent a novel therapeutic strategy for the treatment of HNSCC.
- Hermeking H. The miR-34 family in cancer and apoptosis. Cell Death Differ. 2010;17:193-9 pubmed publisher..In this review, the evidence for a role of miR-34a and miR-34b/c in the apoptotic response of normal and tumor cells is surveyed. ..
- Ichimura A, Ruike Y, Terasawa K, Shimizu K, Tsujimoto G. MicroRNA-34a inhibits cell proliferation by repressing mitogen-activated protein kinase kinase 1 during megakaryocytic differentiation of K562 cells. Mol Pharmacol. 2010;77:1016-24 pubmed publisher..Thus, the results highlight an important regulatory role for miR-34a in the process of megakaryocytic differentiation, especially in the arrest of cell growth, which is a prerequisite for cells to enter differentiation. ..
- Kaller M, Liffers S, Oeljeklaus S, Kuhlmann K, Röh S, Hoffmann R, et al. Genome-wide characterization of miR-34a induced changes in protein and mRNA expression by a combined pulsed SILAC and microarray analysis. Mol Cell Proteomics. 2011;10:M111.010462 pubmed publisher..In summary, miR-34a presumably participates in multiple tumor suppressive pathways by directly and indirectly suppressing the expression of numerous, critical proteins. ..
- Raver Shapira N, Marciano E, Meiri E, Spector Y, Rosenfeld N, Moskovits N, et al. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol Cell. 2007;26:731-43 pubmed..Perturbation of miR-34a expression, as occurs in some human cancers, may thus contribute to tumorigenesis by attenuating p53-dependent apoptosis. ..
- Wang X, Wang H, McCoy J, Banerjee N, Rader J, Broker T, et al. Oncogenic HPV infection interrupts the expression of tumor-suppressive miR-34a through viral oncoprotein E6. RNA. 2009;15:637-47 pubmed publisher..Together, this is the first time a viral oncoprotein has been shown to regulate cellular miRNA expression. Our data have provided new insights into mechanisms by which high-risk HPVs contribute to the development of cervical cancer...
- Tazawa H, Tsuchiya N, Izumiya M, Nakagama H. Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc Natl Acad Sci U S A. 2007;104:15472-7 pubmed..Abrogation of miR-34a function could contribute to aberrant cell proliferation, leading to colon cancer development. ..
- Tarasov V, Jung P, Verdoodt B, Lodygin D, Epanchintsev A, Menssen A, et al. Differential regulation of microRNAs by p53 revealed by massively parallel sequencing: miR-34a is a p53 target that induces apoptosis and G1-arrest. Cell Cycle. 2007;6:1586-93 pubmed..siRNAs corresponding to p53-induced miRNAs may have potential as cancer therapeutic agents as RNA interference based therapies are currently emerging. ..
- Asslaber D, Pinon J, Seyfried I, Desch P, Stöcher M, Tinhofer I, et al. microRNA-34a expression correlates with MDM2 SNP309 polymorphism and treatment-free survival in chronic lymphocytic leukemia. Blood. 2010;115:4191-7 pubmed publisher..Further, overexpression of miR-34a in primary B-CLL cells induced apoptosis. These findings suggest miR-34a as a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in B-CLL. ..
- Zauli G, Voltan R, di Iasio M, Bosco R, Melloni E, Sana M, et al. miR-34a induces the downregulation of both E2F1 and B-Myb oncogenes in leukemic cells. Clin Cancer Res. 2011;17:2712-24 pubmed publisher..Knockdown experiments with siRNA for p53 and E2F1 and overexpression experiments with miR34a were conducted to elucidate the role of these pathways in promoting B-Myb downregulation...
- Jain A, Allton K, Iacovino M, Mahen E, Milczarek R, Zwaka T, et al. p53 regulates cell cycle and microRNAs to promote differentiation of human embryonic stem cells. PLoS Biol. 2012;10:e1001268 pubmed publisher..These studies underscore the importance of a p53-regulated network in determining the human stem cell state. ..