Abstract:
:Myotonic dystrophy type 1 (DM1) is the most common type of adult muscular dystrophy caused by the expanded triple-nucleotides (CUG) repeats. Myoblast in DM1 displayed many defects, including defective myoblast differentiation, ribonuclear foci, and aberrant alternative splicing. Despite many were revealed to function in DM1, microRNAs that regulated DM1 via directly targeting the expanded CUG repeats were rarely reported. Here we discovered that miR-322/-503 rescued myoblast defects in DM1 cell model by targeting the expanded CUG repeats. First, we studied the function of miR-322/-503 in normal C2C12 myoblast cells. Downregulation of miR-322/-503 significantly hindered the myoblast differentiation, while miR-322/-503 overexpression promoted the process. Next, we examined the role of miR-322/-503 in the DM1 C2C12 cell model. miR-322/-503 was downregulated in the differentiation of DM1 C2C12 cells. When we introduced ectopic miR-322/-503 expression into DM1 C2C12 cells, myoblast defects were almost fully rescued, marked by significant improvements of myoblast differentiation and repressions of ribonuclear foci formation and aberrant alternative splicing. Then we investigated the downstream mechanism of miR-322/-503 in DM1. Agreeing with our previous work, Celf1 was proven to be miR-322/-503's target. Celf1 knockdown partially reproduced miR-322/-503's function in rescuing DM1 C2C12 differentiation but was unable to repress ribonuclear foci, suggesting other targets of miR-322/-503 existed in the DM1 C2C12 cells. As the seed regions of miR-322 and miR-503 were complementary to the CUG repeats, we hypothesized that the CUG repeats were the target of miR-322/-503. Through expression tests, reporter assays, and colocalization staining, miR-322/-503 was proved to directly and specifically target the expanded CUG repeats in the DM1 cell model rather than the shorter ones in normal cells. Those results implied a potential therapeutic function of miR-322/-503 on DM1, which needed further investigations in the future.
journal_name
Cell Death Disjournal_title
Cell death & diseaseauthors
Shen X,Xu F,Li M,Wu S,Zhang J,Wang A,Xu L,Liu Y,Zhu Gdoi
10.1038/s41419-020-03112-6subject
Has Abstractpub_date
2020-10-22 00:00:00pages
891issue
10issn
2041-4889pii
10.1038/s41419-020-03112-6journal_volume
11pub_type
杂志文章abstract::Homeodomain-interacting protein kinase 2 (HIPK2) is a multitalented coregulator of an increasing number of transcription factors and cofactors involved in cell death and proliferation in several organs and systems. As Hipk2(-/-) mice show behavioral abnormalities consistent with cerebellar dysfunction, we investigated...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2015.298
更新日期:2015-12-03 00:00:00
abstract::Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential an...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.41
更新日期:2011-05-19 00:00:00
abstract::Catecholaminergic Polymorphic Ventricular Tachycardia type 2 (CPVT2) is a highly lethal recessive arrhythmogenic disease caused by mutations in the calsequestrin-2 (CASQ2) gene. We have previously demonstrated that viral transfer of the wild-type (WT) CASQ2 gene prevents the development of CPVT2 in a genetically induc...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.304
更新日期:2016-10-06 00:00:00
abstract::Non-small cell lung cancer (NSCLC) has the highest incidence of cancer-related death worldwide and a high medical need for more effective therapies. Small-molecule inhibitors of the bromodomain and extra terminal domain (BET) family such as JQ1, I-BET762 and OTX-015 are active in a wide range of different cancer types...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.271
更新日期:2016-09-08 00:00:00
abstract::Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.485
更新日期:2014-11-20 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Cell death & disease
pub_type: 杂志文章,撤回出版物
doi:10.1038/s41419-019-1866-9
更新日期:2019-08-22 00:00:00
abstract::After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we sho...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2011.59
更新日期:2011-06-23 00:00:00
abstract::Microglia serve as the innate immune cells of the central nervous system (CNS) by providing continuous surveillance of the CNS microenvironment and initiating defense mechanisms to protect CNS tissue. Upon injury, microglia transition into an activated state altering their transcriptional profile, transforming their m...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-03084-7
更新日期:2020-10-23 00:00:00
abstract::Many recent studies have uncovered the necessary role for the receptor-interacting protein kinase 1 (RIP1) in regulating apoptosis and necrosis that cells undergo in response to various cellular stresses. However, the functional significance of RIP1 in promoting cancer cells survival remains poorly understood. Here, w...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0714-7
更新日期:2018-06-07 00:00:00
abstract::Parkin (Park2), a RING-between-RING-type E3 ubiquitin ligase, has been implicated in regulating NF-κB. Mutations in Parkin are associated with Parkinson's disease. Here we investigated the interaction of Parkin with Receptor-interacting protein kinase 1 (RIPK1) kinase, a key mediator of multiple signaling pathways act...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0770-z
更新日期:2018-06-28 00:00:00
abstract::HFM1 (helicase for meiosis 1) is widely recognized as an ATP-dependent DNA helicase and is expressed mainly in germ-line cells. HFM1 is a candidate gene of premature ovarian failure (POF), hence it is also known as POF9. However, the roles of HFM1 in mammalian oocytes remain uncertain. To investigate the functions of ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2697-4
更新日期:2020-06-30 00:00:00
abstract::The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2012.139
更新日期:2012-10-11 00:00:00
abstract::Growing evidence indicates that cell adhesion to extracellular matrix (ECM) plays an important role in cancer chemoresistance. Leukemic T cells express several adhesion receptors of the β1 integrin subfamily with which they interact with ECM. However, the role of β1 integrins in chemoresistance of T-cell acute lymphob...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1593-2
更新日期:2019-05-01 00:00:00
abstract::Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in si...
journal_title:Cell death & disease
pub_type: 临床试验,杂志文章
doi:10.1038/cddis.2014.256
更新日期:2014-06-26 00:00:00
abstract::The δ opioid receptor (DOR) is involved in the regulation of malignant transformation and tumor progression of hepatocellular carcinoma (HCC). However, regulation of the DOR in HCC remains poorly defined. We found that miR-874 was identified as a negative regulator of the DOR, which is a direct and functional target o...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0131-3
更新日期:2018-01-26 00:00:00
abstract::Hepatocellular carcinoma (HCC) represents the second cause of cancer-related mortality worldwide and is associated with poor prognosis, especially in patients not amenable for curative treatments. The multi-kinase inhibitor sorafenib represents the first-line treatment option for advanced HCC; nevertheless, its effect...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0076-6
更新日期:2018-01-05 00:00:00
abstract::Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0225-y
更新日期:2018-02-07 00:00:00
abstract::New bone anabolic agents for the effective treatment of bone metabolic diseases like osteoporosis are of high clinical demand. In the present study, we reveal the function of salt-inducible kinase 1 (SIK1) in regulating osteoblast differentiation. Gene knockdown of SIK1 but not of SIK2 or SIK3 expression in primary pr...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-019-1915-4
更新日期:2019-10-31 00:00:00
abstract::Thioredoxin-interacting protein (TXNIP) is involved in oxidative stress and apoptosis in diabetic retinopathy. However, the role of TXNIP in the removal of damaged mitochondria (MT) via mitophagy, a process of macroautophagy, remains unexplored. Here we investigate the associated cellular and molecular mechanisms unde...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.190
更新日期:2017-05-11 00:00:00
abstract::Protein kinase C (PKC) isozymes play major roles in human diseases, including cancer. Yet, the poor understanding of isozymes-specific functions and the limited availability of selective pharmacological modulators of PKC isozymes have limited the clinical translation of PKC-targeting agents. Here, we report the first ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0154-9
更新日期:2018-01-18 00:00:00
abstract::Plastic phenotype convention between glioma stem cells (GSCs) and non-stem tumor cells (NSTCs) significantly fuels glioblastoma heterogeneity that causes therapeutic failure. Recent progressions indicate that glucose metabolic reprogramming could drive cell fates. However, the metabolic pattern of GSCs and NSTCs and i...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1015-x
更新日期:2018-09-24 00:00:00
abstract::Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 ass...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2010.86
更新日期:2010-12-16 00:00:00
abstract::Sepsis is a systemic inflammation caused by infection. The balance between M1-M2 macrophage polarization has an essential role in the pathogenesis of sepsis. However, the exact mechanism underlying macrophage polarization is unclear. We previously showed that levels of malignant fibrous histiocytoma amplified sequence...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2017.102
更新日期:2017-05-04 00:00:00
abstract::Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors with poor survival. It is urgent to search for new efficient drugs with good stability and safety for clinical therapy. This study aims to identify potential anticancer drugs from a compound library consisting of 429 natural products....
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-020-2730-7
更新日期:2020-07-13 00:00:00
abstract::Correction to: NPG Asia Materials (2018) https://doi.org/10.1038/s41427-018-0014-9 published online on 16 April 2018. ...
journal_title:Cell death & disease
pub_type: 已发布勘误
doi:10.1038/s41419-018-0639-1
更新日期:2018-05-24 00:00:00
abstract::Resistin is an adipokine that is associated with obesity, inflammation, and various cancers. Chondrosarcomas are primary malignant bone tumors that have a poor prognosis. VEGF-A is a critical angiogenic factor that is known to promote angiogenesis and metastasis in chondrosarcoma. It is unknown as to whether resistin ...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-1241-2
更新日期:2019-01-10 00:00:00
abstract::Although it is becoming increasingly evident that maternal starvation during pregnancy can have permanent effects on a range of physiological processes in the offspring, scant information is available about the consequence of such condition for oogenesis and hence for lifetime reproductive success of progeny in mammal...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-018-0492-2
更新日期:2018-05-01 00:00:00
abstract::Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of a...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2016.465
更新日期:2017-01-26 00:00:00
abstract::The control of glucose metabolism and the cell cycle must be coordinated in order to guarantee sufficient ATP and anabolic substrates at distinct phases of the cell cycle. The family of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases (PFKFB1-4) are well established regulators of glucose metabolism via their synt...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/cddis.2014.292
更新日期:2014-07-17 00:00:00
abstract::Osteoclasts are absorptive cells that play a critical role in homeostatic bone remodeling and pathological bone resorption. Emerging evidence suggests an important role of epigenetic regulation in osteoclastogenesis. In this study, we investigated the role of DOT1L, which regulates gene expression epigenetically by hi...
journal_title:Cell death & disease
pub_type: 杂志文章
doi:10.1038/s41419-017-0040-5
更新日期:2018-01-18 00:00:00