Abstract:
:Deregulation of microRNAs (miRNAs) and c-Myc (Myc) contributes to hepatocellular carcinoma (HCC) progression, but how miRNAs and Myc regulate each other in hepatocarcinogenesis is still poorly understood. Using a functional screen, we identified miR-129-5p as a miRNA that inhibits HCC cell growth. miR-129-5p targets the mitochondrial matrix protein pyruvate dehydrogenase kinase 4 (PDK4), which leads to decreased phosphorylation of the E1α subunit of pyruvate dehyrogenase (PDH) complex, inhibition of glycolysis, retarded tumor growth, and impaired lung colonization. Enforced expression of PDK4 refractory to inhibition by miR-129-5p rescued all of these phenotypes. Targeting PDK4 by shRNA recapitulated the effects caused by miR-129-5p. miR-129-5p is transcriptionally repressed by a complex comprised of Myc, histone deacetylase 3 (HDAC3), and enhancer of zeste 2 polycomb repressive complex 2 (EZH2). Levels of miR-129-5p negatively correlated with clinical stages in human HCC. Restoring miR-129-5p expression suppressed the diethylnitrosamine (DEN)-induced hepatocarcinogenesis in mice. Thus, we concluded that miR-129-5p, which is a negative target of Myc, blocks glycolysis to retard hepatocarcinogenesis via targeting PDK4. The critical link between miR-129-5p and PDK4 in the progression of HCC suggests potential points of therapeutic intervention for this disease.
journal_name
J Mol Cell Bioljournal_title
Journal of molecular cell biologyauthors
Han H,Li W,Shen H,Zhang J,Zhu Y,Li Ydoi
10.1093/jmcb/mjw010subject
Has Abstractpub_date
2016-10-01 00:00:00pages
400-410issue
5eissn
1674-2788issn
1759-4685pii
mjw010journal_volume
8pub_type
杂志文章abstract::Our earlier studies have demonstrated that the cigarette smoke in the form of cigarette smoke condensate (CSC) causes growth arrest of a mouse spermatocyte cell line [GC-2spd(ts)] through activation of the AHR-NRF2 pathway. The present study demonstrates the CSC-activated p38 and ERK MAPK signaling in GC-2spd(ts) via ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mju049
更新日期:2015-02-01 00:00:00
abstract::Haploid pluripotent stem cells, such as haploid embryonic stem cells (haESCs), facilitate the genetic study of recessive traits. In vitro, fish haESCs maintain haploidy in both undifferentiated and differentiated states, but whether mammalian haESCs can preserve pluripotency in the haploid state has not been tested. H...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv044
更新日期:2015-08-01 00:00:00
abstract::Mammalian fertilization involves membrane events-adhesion, fusion, sperm engulfment, membrane block to polyspermy-whose causes remain largely unknown. Recently, specific oscillations of the sperm in contact with the egg were shown to be necessary for fusion. Using a microfluidic chip to impose the venue for the encoun...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy005
更新日期:2018-12-01 00:00:00
abstract::Long thought to be the glue responsible for holding sister chromatids together, cohesin has been found to be stickier than previously thought. Recent discoveries point to cohesin having a role in transcription regulation by mediating long-distance intra-chromosomal interactions. ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjp014
更新日期:2009-12-01 00:00:00
abstract::Normal tissues are organized in a hierarchical model, whereas at the apex of these hierarchies reside stem cells (SCs) capable of self-renewal and of producing differentiated cellular progenies, leading to normal development and homeostasis. Alike, tumors are organized in a hierarchical manner, with cancer SCs residin...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjz022
更新日期:2019-07-19 00:00:00
abstract::Mutations of epigenetic regulators are pervasive in human tumors. ASXL1 is frequently mutated in myeloid malignancies. We previously found that ASXL1 forms together with BAP1 a complex that can deubiquitinylate mono-ubiquitinylated lysine 119 on histone H2A (H2AK119ub1), a Polycomb repressive mark. However, a complete...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa011
更新日期:2020-09-01 00:00:00
abstract::Although cancer and neurodegenerative disease are two distinct pathological disorders, emerging evidence indicates that these two types of disease share common mechanisms of genetic and molecular abnormalities. Recent studies show that individual microRNAs (miRNAs) could be involved in the pathology of both diseases, ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjq058
更新日期:2011-06-01 00:00:00
abstract::Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa060
更新日期:2020-10-30 00:00:00
abstract::Understanding the mechanism of how cholangiocytes (liver ductal cells) are activated upon liver injury and specified to hepatocytes would permit liver regenerative medicine. Here we achieved long-term in vitro expansion of mouse liver organoids by modulating signaling pathways with a combination of three small-molecul...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa010
更新日期:2020-08-01 00:00:00
abstract::SRY-related HMG-box gene 2 (SOX2) is one of the key regulatory genes that maintain the pluripotency and self-renewal properties in embryonic stem cells. Here we used immunohistochemistry to analyze the expression of SOX2 in human prostate tissues and found it contributed to tumorigenesis and correlated with histologic...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjr002
更新日期:2011-08-01 00:00:00
abstract::Dying cells actively attract professional phagocytes by sending out soluble 'find-me' signals. The characterization and identification of the corresponding molecular entities have revealed that 'find-me' signals come in different flavors, including peptides, proteins, lipids and complex structures, such as apoptotic m...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjp045
更新日期:2010-04-01 00:00:00
abstract::Type 2 immune response has been shown to facilitate cold-induced thermogenesis and browning of white fat. However, whether alternatively activated macrophages produce catecholamine and substantially promote adaptive thermogenesis in adipose tissue remains controversial. Here, we show that tyrosine hydroxylase (TyrH), ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx046
更新日期:2017-10-01 00:00:00
abstract::The Hippo signalling pathway has a crucial role in growth control during development, and its dysregulation contributes to tumorigenesis. Recent studies uncover multiple upstream regulatory inputs into Hippo signalling, which affects phosphorylation of the transcriptional coactivator Yki/YAP/TAZ by Wts/Lats. Here we i...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw036
更新日期:2016-08-01 00:00:00
abstract::We previously identified that hepatitis B virus (HBV) encodes a microRNA (HBV-miR-3) that restrains HBV replication by targeting the HBV transcript. However, whether HBV-miR-3 affects host innate immunity to modulate HBV replication remains unclear. Here, we examined the vital functions of HBV-miR-3 in the innate immu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjz104
更新日期:2020-05-18 00:00:00
abstract::Local signaling events at synapses or axon terminals are communicated to the nucleus to elicit transcriptional responses, and thereby translate information about the external environment into internal neuronal representations. This retrograde signaling is critical to dendritic growth, synapse development, and neuronal...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa058
更新日期:2020-10-26 00:00:00
abstract::Although genome-wide association studies (GWAS) have successfully identified thousands of genomic loci associated with hundreds of complex traits in the past decade, the debate about such problems as missing heritability and weak interpretability has been appealing for effective computational methods to facilitate the...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjx059
更新日期:2017-12-01 00:00:00
abstract::Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem neurons. Zfhx4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse brainstem. Mice lacking Zfhx4 died shortly after birth from an apparent inabil...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa081
更新日期:2021-01-20 00:00:00
abstract::Triple-negative breast cancer (TNBC), characterized by the lack of expression of the estrogen receptor, the progesterone receptor, and the human epidermal growth factor receptor 2, is an aggressive form of cancer that conveys unpredictable and poor prognosis due to limited treatment options and lack of effective targe...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy041
更新日期:2018-08-01 00:00:00
abstract::Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 g...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjt011
更新日期:2013-08-01 00:00:00
abstract::The mammalian target of rapamycin (mTOR) is a protein kinase that plays key roles in cellular regulation. It forms complexes with additional proteins. The best-understood one is mTOR complex 1 (mTORC1). The regulation and cellular functions of mTORC1 have been the subjects of intense study; despite this, many question...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjq038
更新日期:2011-08-01 00:00:00
abstract::Advances in functional genomics have led to discovery of a large group of previous uncharacterized long non-coding RNAs (lncRNAs). Emerging evidence indicates that lncRNAs may serve as master gene regulators through various mechanisms. Dysregulation of lncRNAs is often associated with a variety of human diseases inclu...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mju013
更新日期:2014-06-01 00:00:00
abstract::Homoeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how t...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjw041
更新日期:2017-04-01 00:00:00
abstract::X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression. In female mammals, mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript (XIST) is essential for initiation of X chromosome inactivation upon differ...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjy074
更新日期:2019-09-19 00:00:00
abstract::The mouse double minute 4 (MDM4) is emerging from the shadow of its more famous relative MDM2 and is starting to steal the limelight, largely due to its therapeutic possibilities. MDM4 is a vital regulator of the tumor suppressor p53. It restricts p53 transcriptional activity and also, at least in development, facilit...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章,评审
doi:10.1093/jmcb/mjz007
更新日期:2019-03-01 00:00:00
abstract::E-selectin is a cell-adhesion molecule of the vascular endothelium that promotes essential leukocyte rolling in the early inflammatory response by binding to glycoproteins containing the tetrasaccharide sialyl Lewis(x) (sLe(x)). Efficient leukocyte recruitment under vascular flow conditions depends on an increased lif...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjv046
更新日期:2016-02-01 00:00:00
abstract::TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis (ALS) cases, suggesting a central pathogenic role of this regulatory protein. Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy. The ubiquitin E3 ligase R...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjaa072
更新日期:2021-01-02 00:00:00
abstract::Human colon carcinomas (CCs) represent a growing worldwide problem. One of the pathways that has been negatively implicated in the genesis of CCs is triggered by bone morphogenetic protein (BMP) ligands, which activate BMP receptors leading to the function of SMAD proteins in the nucleus. BMP signaling is altered in f...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjq035
更新日期:2010-12-01 00:00:00
abstract::Mycobacterium tuberculosis is one of the most notorious killers worldwide. These pathogens have evolved to infect human beings in a so-called dormant form that is extremely difficult to treat. New work, however, suggests that mycobacterial proteasomes, multicomponent structures that protect the microbe from damaging e...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjp053
更新日期:2010-08-01 00:00:00
abstract::MEK inhibitor has been highlighted as a promising anti-tumor drug but its effect has been reported as varying over a wide range depending on patho-physiological conditions. In this study, we employed a systems approach by combining biochemical experimentation with in silico simulations to investigate the resistance me...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjs021
更新日期:2012-06-01 00:00:00
abstract::The activity of dopaminergic neurons are thought to be increased by stimuli that predict reward and decreased by stimuli that predict aversive outcomes. Recent work by Matsumoto and Hikosaka challenges this model by asserting that stimuli associated with either rewarding or aversive outcomes increase the activity of d...
journal_title:Journal of molecular cell biology
pub_type: 杂志文章
doi:10.1093/jmcb/mjp010
更新日期:2009-10-01 00:00:00