MicroRNA-1 Regulates Cardiomyocyte Apoptosis by Targeting Bcl-2

Tang, Yanchao; Zheng, Jie; Sun, Yan; Wu, Zonggui; Liu, Zhimin; Huang, Guangwen

doi:10.1536/ihj.50.377

Cited by 230 publications

(176 citation statements)

References 8 publications

(14 reference statements)

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“…This result is in contrast with two previous studies in myocardial cells showing an upregulation of miR-1 on H 2 O 2 exposure. 21,22 Interestingly, miR-1 is known to promote myogenic differentiation 23 and our finding on miR-1 downmodulation by H 2 O 2 is in agreement with ROS ability to inhibit myogenic differentiation. 3 miR-200 family has been extensively studied in the epithelial-to-mesenchimal transition (EMT) of cancer cells; 14 in EMT miR-200 family downmodulation enhances cancer aggressiveness and metastases, whereas reintroduction of miR-200 family miRNAs in some tumors inhibits their growth.…”

Section: Discussionsupporting

confidence: 86%

miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition

et al. 2011

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We examined the effect of reactive oxygen species (ROS) on MicroRNAs (miRNAs) expression in endothelial cells in vitro, and in mouse skeletal muscle following acute hindlimb ischemia. Human umbilical vein endothelial cells (HUVEC) were exposed to 200 lM hydrogen peroxide (H 2 O 2 ) for 8 to 24 h; miRNAs profiling showed that miR-200c and the co-transcribed miR-141 increased more than eightfold. The other miR-200 gene family members were also induced, albeit to a lower level. Furthermore, miR-200c upregulation was not endothelium restricted, and occurred also on exposure to an oxidative stress-inducing drug: 1,3-bis(2 chloroethyl)-1nitrosourea (BCNU). miR-200c overexpression induced HUVEC growth arrest, apoptosis and senescence; these phenomena were also induced by Reactive oxygen species (ROS) play a causal role in a variety of cardiovascular diseases, including ischemia, ischemia/ reperfusion (I/R) injury, diabetic vasculopathy and atherosclerosis, and in aging. 1-3 ROS, which include H 2 O 2 , superoxide anion and hydroxyl radicals have been demonstrated to inhibit cell growth and to induce cell death and senescence. 1 MicroRNAs (miRNAs) are small non-coding RNAs, usually 21-23 nucleotides long, which regulate the stability and/or the translational efficiency of target messenger RNAs (mRNAs). 4 They appear to be closely conserved across species and to them have been ascribed diverse functions, including regulation of proliferation, differentiation, senescence and death. 5 The objective of the present work was to establish the effect of ROS on miRNAs expression, and to determine whether miRNAs modulate endothelial cells (EC) response to oxidative stress. In light of the important role that tumor suppressor proteins retinoblastoma (pRb) and p53 have in responses to ROS, we examined their contribution to miRNAs expression on oxidative stress exposure. The retinoblastoma family, which includes pRb, p130 and p107, is an integral part of the mechanism that regulates proliferation and senescence via phosphorylation-sensitive interactions, regulating either positively or negatively E2F transcription factors family. 6 H 2 O 2 causes rapid pRb dephosphorylation by the activity of protein phosphatase 2A 7,8 and successively, by the increase of p53 protein, which in turns upregulates the CDK inhibitor p21 Waf1/Cip1/Sdi1 (p21). 7 The ROS effect on miRNAs expression was also evaluated in vivo, in a mouse model of hindlimb ischemia, both in wild-type (wt) and in p66 ShcA -null (p66 ShcAÀ/À ) mice. The mammalian adaptor protein p66 ShcA regulates ROS metabolism and apoptosis. The cytoplasmic fraction of p66 ShcA is phosphorylated in serine 36 residue in response to several stimuli, including UV and H 2 O 2 . 9 Moreover, a fraction of p66 ShcA is localized in the mitochondria and functions as a redox enzyme that generates ROS; 10 accordingly p66 ShcAÀ/À mice display lower levels of intracellular ROS 9 and decreased oxidative stress levels and tissue damage following ischemia and I/R injury. 2,3 In the present work, we show tha...

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Section: Discussionsupporting

confidence: 86%

miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition

et al. 2011

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“…11 In a recent study, the regulatory roles of miR146b-5p in erythropoiesis and megakaryopoiesis have been reported. 40 MiR-1 has BCL2 as its target, 41 and circulating miR-1 is a potential novel biomarker in acute myocardial infarction. 42 MiR-1 exhibits anti-inflammatory roles in asthma mouse models and in inflammatory myopathies.…”

Section: Discussionmentioning

confidence: 99%

A plasma microRNA signature as a biomarker for acquired aplastic anemia

et al. 2016

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“…Another group reported that the mRNA and protein levels of transforming growth factor-␤ and SMAD3 are decreased by a virus-encoded microRNA, miR-LAT (23). The mRNA and protein levels of Bcl-2 are also down-regulated by miR-1 (24). Thus, our result is not unusual and provides new evidence to support the conclusion that miRNAs regulate not only the stability and translation but also the transcription of target mRNAs; the latter is most likely via an indirect mechanism.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-206 Targets notch3, Activates Apoptosis, and Inhibits Tumor Cell Migration and Focus Formation

Song

Zhang

Wang

2009

Journal of Biological Chemistry

191

179

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MicroRNAs contribute to cancer development by acting as oncogenes or tumor suppressor genes. However, only a few microRNA target genes were determined. We identified a nearly perfect complementarity between miR-206 and the 3-untranslated regions of both mouse and human notch3. Expression of miR-206 decreased the luciferase activity dose-dependently when cotransfected with the mouse or human notch3 3-untranslated region-luciferase reporter containing the miR-206 target site in HeLa cells. This suppression was relieved by deletion and mutation of the miR-206-binding site and was partially recovered by expression of notch3 or by a specific inhibitor of miR-206. Interestingly, overexpression of miR-206 decreased the levels of both Notch3 protein and mRNA. Expression of miR-206 markedly induced apoptotic cell death and blocked the anti-apoptotic activity of Notch3. In addition, ectopic expression of miR-206 inhibited HeLa cell migration and focus formation. Therefore, we identified miR-206 as a pro-apoptotic activator of cell death, which was associated with its inhibition of notch3 signaling and tumor formation. The inhibition of cancer cell migration and focus formation by miR-206 strongly suggests that miR-206 may function as a novel tumor suppressor. MicroRNAs (miRNAs)2 regulate gene expression by binding to the 3Ј-untranslated regions (3Ј-UTRs) of specific mRNAs (1) and play important roles in development, proliferation, and differentiation (2-4). Recent studies revealed the involvement of miRNAs in apoptosis signaling (5). For instance, miR-15 and miR-16 have been shown to induce apoptosis by targeting Bcl-2 (6). miR-34a can be regulated by p53, which promotes apoptosis (7,8). Despite the growing evidence for their importance in carcinogenesis (9), limited information is available about their function in human cancers. The future challenges are to identify the biological targets of miRNAs and the signaling pathways they regulate during oncogenesis.Early studies identified miR-206 as a skeletal musclespecific miRNA involved in muscle development (10 -12). Recent studies showed that miR-206 targets the estrogen receptor (13) and is down-regulated in estrogen receptorpositive breast cancer (14). It is thus postulated that miR-206 may be associated with breast cancer metastasis (15). In addition to its high expression in muscle, miR-206 was also reported to be expressed in brain associated with schizophrenia (16) and in brown adipocytes (17). The level of miR-206 is increased in bone marrow-derived DC19ϩ WM cells associated with Waldenström macroglobulinemia (18). Despite a broader tissue-specific expression than originally anticipated, the physiological function of miR-206 in cancer progression remains largely unknown.In this study, we report several novel findings. We identify notch3 (Notch homolog 3) as a novel miR-206 target. We reveal miR-206 as a potent apoptotic cell death inducer via cross-talk with notch3. We further show that miR-206 inhibits tumor cell migration and focus formation. Our study suggests mi...

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MicroRNA-1 Regulates Cardiomyocyte Apoptosis by Targeting Bcl-2

Cited by 230 publications

References 8 publications

miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition

miR-200c is upregulated by oxidative stress and induces endothelial cell apoptosis and senescence via ZEB1 inhibition

A plasma microRNA signature as a biomarker for acquired aplastic anemia

MicroRNA-206 Targets notch3, Activates Apoptosis, and Inhibits Tumor Cell Migration and Focus Formation

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