HCSGD entry for HRAS
1. General information
| Official gene symbol | HRAS |
|---|---|
| Entrez ID | 3265 |
| Gene full name | v-Ha-ras Harvey rat sarcoma viral oncogene homolog |
| Other gene symbols | C-BAS/HAS C-H-RAS C-HA-RAS1 CTLO H-RASIDX HAMSV HRAS1 K-RAS N-RAS RASH1 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000139 | Golgi membrane | IEA | cellular_component |
| GO:0000165 | MAPK cascade | TAS | biological_process |
| GO:0000186 | Activation of MAPKK activity | TAS | biological_process |
| GO:0001934 | Positive regulation of protein phosphorylation | IDA | biological_process |
| GO:0003924 | GTPase activity | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005525 | GTP binding | IDA | molecular_function |
| GO:0005634 | Nucleus | IEA | cellular_component |
| GO:0005737 | Cytoplasm | TAS | cellular_component |
| GO:0005794 | Golgi apparatus | IDA | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0005886 | Plasma membrane | IDA TAS | cellular_component |
| GO:0006897 | Endocytosis | IEA | biological_process |
| GO:0006935 | Chemotaxis | TAS | biological_process |
| GO:0007050 | Cell cycle arrest | IDA IMP | biological_process |
| GO:0007093 | Mitotic cell cycle checkpoint | IDA | biological_process |
| GO:0007165 | Signal transduction | NAS | biological_process |
| GO:0007166 | Cell surface receptor signaling pathway | TAS | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0007264 | Small GTPase mediated signal transduction | TAS | biological_process |
| GO:0007265 | Ras protein signal transduction | IDA TAS | biological_process |
| GO:0007268 | Synaptic transmission | TAS | biological_process |
| GO:0007411 | Axon guidance | TAS | biological_process |
| GO:0007596 | Blood coagulation | TAS | biological_process |
| GO:0008022 | Protein C-terminus binding | IPI | molecular_function |
| GO:0008283 | Cell proliferation | IEA | biological_process |
| GO:0008284 | Positive regulation of cell proliferation | IDA | biological_process |
| GO:0008285 | Negative regulation of cell proliferation | IDA | biological_process |
| GO:0008286 | Insulin receptor signaling pathway | TAS | biological_process |
| GO:0008542 | Visual learning | IEA | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0009887 | Organ morphogenesis | TAS | biological_process |
| GO:0010629 | Negative regulation of gene expression | IDA | biological_process |
| GO:0030036 | Actin cytoskeleton organization | IEA | biological_process |
| GO:0030335 | Positive regulation of cell migration | IDA | biological_process |
| GO:0032228 | Regulation of synaptic transmission, GABAergic | IEA | biological_process |
| GO:0032855 | Positive regulation of Rac GTPase activity | IDA | biological_process |
| GO:0034259 | Negative regulation of Rho GTPase activity | IDA | biological_process |
| GO:0035022 | Positive regulation of Rac protein signal transduction | IEA | biological_process |
| GO:0035176 | Social behavior | IEA | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0043406 | Positive regulation of MAP kinase activity | IDA | biological_process |
| GO:0043410 | Positive regulation of MAPK cascade | IDA | biological_process |
| GO:0043524 | Negative regulation of neuron apoptotic process | IEA | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045740 | Positive regulation of DNA replication | IDA | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IDA | biological_process |
| GO:0046330 | Positive regulation of JNK cascade | IDA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048169 | Regulation of long-term neuronal synaptic plasticity | IEA | biological_process |
| GO:0048471 | Perinuclear region of cytoplasm | IEA | cellular_component |
| GO:0050679 | Positive regulation of epithelial cell proliferation | IMP | biological_process |
| GO:0050900 | Leukocyte migration | TAS | biological_process |
| GO:0051146 | Striated muscle cell differentiation | IEA | biological_process |
| GO:0051291 | Protein heterooligomerization | IEA | biological_process |
| GO:0070374 | Positive regulation of ERK1 and ERK2 cascade | IDA | biological_process |
| GO:0090303 | Positive regulation of wound healing | IDA | biological_process |
| GO:0090398 | Cellular senescence | IDA | biological_process |
| GO:0097193 | Intrinsic apoptotic signaling pathway | IEA | biological_process |
| GO:1900029 | Positive regulation of ruffle assembly | IDA | biological_process |
| GO:2000251 | Positive regulation of actin cytoskeleton reorganization | IDA | biological_process |
| GO:2000630 | Positive regulation of miRNA metabolic process | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0064206071 | 0.8221789978 | 0.2116718905 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.1934978268 |
| GSE13712_SHEAR | Up | 0.2956080583 |
| GSE13712_STATIC | Up | 0.1993091041 |
| GSE19018 | Up | 0.2620557208 |
| GSE19899_A1 | Up | 0.4107268492 |
| GSE19899_A2 | Up | 0.9945000955 |
| PubMed_21979375_A1 | Up | 3.0694259528 |
| PubMed_21979375_A2 | Up | 0.8463184780 |
| GSE35957 | Down | -0.4827870487 |
| GSE36640 | Down | -0.6982073060 |
| GSE54402 | Up | 1.1753141242 |
| GSE9593 | Up | 0.0723885653 |
| GSE43922 | Up | 1.8474022971 |
| GSE24585 | Down | -0.4540714861 |
| GSE37065 | Down | -0.0652029825 |
| GSE28863_A1 | Down | -0.1937052643 |
| GSE28863_A2 | Down | -0.1326770938 |
| GSE28863_A3 | Up | 0.0380309206 |
| GSE28863_A4 | Up | 0.1360233417 |
| GSE48662 | Up | 0.2713494041 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Name | Drug | Accession number |
|---|---|---|
| Hexane-1,6-Diol | DB02210 | EXPT01731 |
| Trifluoroethanol | DB03226 | EXPT01368 |
| Guanosine-5'-Triphosphate | DB04137 | EXPT01660 |
| Guanosine-5'-Diphosphate | DB04315 | EXPT01573 |
| N,N'-DIMETHYL-N-(ACETYL)-N'-(7-NITROBENZ-2-OXA-1,3-DIAZOL-4-YL)ETHYLENEDIAMINE | DB08751 | - |
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-181d-5p | MIMAT0002821 | MIRT006548 | FACS//Immunohistochemistry//Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 22207524 |
| hsa-let-7a-5p | MIMAT0000062 | MIRT004471 | Luciferase reporter assay | Functional MTI | 18083101 |
| hsa-miR-143-3p | MIMAT0000435 | MIRT005644 | Luciferase reporter assay//Northern blot//qRT-PCR | Functional MTI | 21276449 |
| hsa-miR-181a-5p | MIMAT0000256 | MIRT005880 | Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay | Functional MTI | 21167132 |
| hsa-miR-615-3p | MIMAT0003283 | MIRT040422 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-let-7a-5p | MIMAT0000062 | NA | hsa-let-7a | {Western blot} | {overexpression by miRNA precursor transfection} | 20005451 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 28 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27352265 | HRAS is a proto-oncogene and has potential to cause cancer in several organs including the bladder |
| 26904954 | Activating K-Ras mutations occurs frequently in pancreatic cancers and is implicated in their development |
| 25452233 | The switching mechanism of NO-mediated signaling includes formation of endogenous NO-derived electrophilic byproducts such as 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), which selectively targets an oncogenic small GTPase H-Ras at Cys-184, leading to cardiac cell senescence via covalent modification (S-guanylation) and activation of H-Ras |
| 24390753 | N-Ras, a known inducer of senescence, was increased in PSC cholangiocytes and in experimentally induced senescent cultured cholangiocytes; inhibition of Ras abrogated experimentally induced senescence and SASP |
| 24390753 | CONCLUSION: Cholangiocyte senescence induced by biliary constituents by way of N-Ras activation is an important pathogenic mechanism in PSC |
| 24390753 | Pharmacologic inhibition of N-Ras with a resultant reduction in cholangiocyte senescence and SASP is a new therapeutic approach for PSC |
| 24213576 | Peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) inhibits skin tumorigenesis through mechanisms that may be dependent on HRAS signaling |
| 23831572 | Here we deleted all three Ras loci (H-Ras, N-Ras and K-Ras) from keratinocytes in vitro as well as specifically from the epidermis in mice using a K5Cre strain |
| 23408353 | Mutational activation of K-Ras is a key genetic event involved in the initiation of pancreatic carcinogenesis |
| 23408353 | However, K-Ras generally fails to transform precursor lesions into invasive cancers due to activation of powerful fail-safe programmes that counteract transformation and growth |
| 23408353 | Moreover, recent work in pancreatic cancer mouse models proposes that inactivation of the CDKN2A tumour suppressor locus is the molecular switch required for senescence evasion and unleashed K-Ras driven malignant transformation in the pancreas |
| 23168260 | Depletion of JMJD2A in the human lung cancer cell line A549 bearing an activated K-Ras allele triggers senescence |
| 22654667 | To date, the identification of drugs to therapeutically inhibit K-RAS have been unsuccessful, suggesting that other approaches are required |
| 22359342 | Expression of oncogenic K-RAS in primary cells elicits oncogene-induced cellular senescence (OIS), a form of growth arrest that potently opposes tumourigenesis |
| 22359342 | PML, a critical OIS mediator, is upregulated by oncogenic K-RAS in vivo and in vitro |
| 22359342 | We demonstrate here that oncogenic K-RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53 |
| 21850009 | HRAS mutants identified in Costello syndrome patients can induce cellular senescence: possible implications for the pathogenesis of Costello syndrome |
| 21850009 | In 2005, we discovered that heterozygous germline mutations in HRAS caused CS |
| 21850009 | Several studies have shown that CS-associated HRAS mutations are clustered in codons 12 and 13, and mutations in other codons have also been identified |
| 21850009 | To examine functional differences among the identified mutations, we characterized a total of nine HRAS mutants, including seven distinct substitutions in codons 12 and 13, p |
| 21850009 | We demonstrated that these mutant HRAS proteins induced senescence when overexpressed in human fibroblasts |
| 21850009 | Our findings suggest that the HRAS mutations identified in CS are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS |
| 21062974 | Notably, we found the DKO mice to be extremely susceptible to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin carcinogenesis that involves oncogenic mutation of the H-ras gene |
| 20388804 | Through the use of RNAi and H-ras induction of cellular senescence, we show that YPEL3 activates cellular senescence downstream of p53 |
| 19501586 | BACKGROUND & AIMS: Differentiated pancreatic acinar cells expressing endogenous levels of mutant K-Ras do not spontaneously develop pancreatic ductal adenocarcinoma (PDAC) |
| 19501586 | We compared the effects of acinar cell expression of mutant K-Ras at endogenous and elevated levels on Ras activity and on the development of PDAC |
| 19501586 | RESULTS: Ras activity was greatly elevated in PDAC cells compared with nontransformed cells expressing endogenous levels of mutant K-Ras |
| 19501586 | Expression of endogenous levels of mutant K-Ras in differentiated acinar cells resulted in moderately elevated Ras activity and in sparse murine pancreatic intraepithelial neoplasias (mPanINs) that did not spontaneously advance to PDAC unless the tumor suppressor p53 was simultaneously deleted |
| 19501586 | In contrast, expression of mutant K-Ras at higher levels generated Ras activity equal to that in PDAC |
| 19421407 | Moreover, lung adenomas initiated by endogenous levels of oncogenic K-Ras presented abundant senescent cells, but undetectable DNA damage signaling |
| 19345325 | Here, we demonstrate that pRb inactivation induces aberrant expression of farnesyl diphosphate synthase, many prenyltransferases, and their upstream regulators sterol regulatory element-binding proteins (SREBPs) in an E2F-dependent manner, leading to enhanced isoprenylation and activation of N-Ras |
| 19345325 | Consequently, elevated N-Ras activity induces DNA damage response and p130-dependent cellular senescence in Rb-deficient cells |
| 19132118 | Constitutively active, 'oncogenic' H-RAS can drive proliferation and transformation in human cancer, or be a potent inducer of cellular senescence |
| 19132118 | In this study we have generated transgenic zebrafish that constitutively express low levels, or can be induced to express high levels, of oncogenic H-RAS |
| 19132118 | We observed that fish carrying the integrated transgene in their germline display several hallmarks of Costello syndrome, a rare genetic disease caused by activating mutations in the gene H-RAS, and can be used as a model for the disease |
| 19132118 | In Costello-like fish, low levels of oncogenic H-RAS expression are associated with both reduced proliferation and an increase in senescence markers in adult progenitor cell compartments in the brain and heart, together with activated DNA damage responses |
| 19132118 | Overexpression of H-RAS through a heat-shock-inducible promoter in larvae led to hyperproliferation, activation of the DNA damage response and tp53-dependent cell cycle arrest |
| 19132118 | Thus, oncogene-induced senescence of adult proliferating cells contributes to the development of Costello syndrome and provides an alternative pathway to transformation in the presence of widespread constitutively active H-RAS expression |
| 16513254 | Similar to overexpression of oncogenic H-ras in the normal human fibroblast, overexpression of IRF3 in human fibroblast BJ cells was shown to decrease cell growth and increase senescence-associated beta-galactosidase activity by activating a p53 tumor suppressor |
| 15489886 | In normal human fibroblasts, senescence induced by oncogenic H-ras displays a nearly identical cellular phenotype to that of replicative senescence, suggesting the activation of a common senescence mechanism |
| 14744771 | The aforementioned changes were observed not only in the replicative senescence but also in the senescence induced by treatment of HDF cells, Mv1Lu, primary culture of human chondrocytes, or Huh7 cells with H-ras virus infection, hydroxyurea, deferoxamine, or H(2)O(2) |
| 14563552 | We transduced cells with amphotropic retroviral constructs containing SV40 T antigen, hTERT, and activated H-ras |
| 12632102 | To investigate whether the two-stage mechanism of cellular aging and immortalization in vitro is involved in the carcinogenesis and immortalization of human colorectal carcinomas, we examined for genetic alterations in the telomeres and in the p53, Rb, and K-ras genes |
| 12632102 | Telomeric repeat-lengths (TRL) were measured by Southern blot analysis, and p53 Rb and K-ras gene variants were detected by PCR based assays |
| 12632102 | K-ras gene mutations and LOH involving the Rb gene were not associated with alterations in TRL |
| 11795508 | In order to investigate signal transduction pathways and related changes of actin cytoskeleton organization in cellular senescence, H-ras double mutants--V12S35, V12G37, and V12C40--were constitutively expressed in human foreskin fibroblast (HDF) |
| 11795508 | Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation |
| 11795508 | In summary, the H-ras double mutant expressers induced premature senescence through the MEK pathway, accompanied by nuclear accumulation of actin and Rac1 proteins, cytoplasmic retention of p-Erk1/2, and marked induction of RhoA expression, suggesting the translocational inefficiency of the intracellular proteins in the senescent HDF cells |
| 11781307 | Functional inactivation of ERalpha by a dominant negative mutant of ERalpha (DNER) in the presence of activated K-Ras 4B mutant arrested the cell cycle at G(0)/G(1), subsequently provoking replicative cell senescence, finally abrogating tumorigenic potential |
| 11781307 | An oncogenic K-Ras 4B mutant significantly increased MDM2 proteins coprecipitated with p53, and suppressed p53 transcriptional activity |
| 11781307 | In turn, DNER exerted its function to decrease MDM2 proteins coprecipitated with p53, followed by the stimulation of p53 activity in the presence of the oncogenic K-Ras 4B mutant |
| 11781307 | The data imply that the ERalpha-AP1 pathway activated by oncogenic K-Ras 4B mutant contributes to the NIH3T3 cells' transformation by modulating p53 transcriptional activity through MDM2 |
| 11208819 | K-ras and p16 aberrations confer poor prognosis in human colorectal cancer |
| 11208819 | PURPOSE: Mutations in the K-ras gene are frequent in human cancer |
| 11208819 | At the clinical level, this may imply a differential behavior for tumors with alternative or cooperative activation of K-ras function and impairment of p16 pathways |
| 11208819 | PATIENTS AND METHODS: We have determined the presence of mutations in the K-ras gene and the methylation status of p16 promoter in a series of 119 prospectively collected colorectal carcinomas |
| 11208819 | RESULTS: K-ras mutations were present in 44 (38%) of 115 cases, and p16 methylation was present in 42 (37%) of 113 cases |
| 11208819 | K-ras and p16 alterations were independent genetic events |
| 11208819 | Presence of K-ras or p16 genetic alterations (analyzed independently) was associated with shorter survival, although differences were not statistically significant |
| 11208819 | Cox analysis of the two variables combined showed a diminished survival as the results of an interaction between p16 and K-ras |
| 11208819 | Alternative alteration of K-ras and p16 genes was an independent prognostic factor in human colorectal cancer in univariate and multivariate analysis |
| 11208819 | CONCLUSION: These results suggest that the combined K-ras and p16 analyses may be of prognostic use in human colorectal cancer |
| 11080532 | In order to investigate the role of signal transduction and the related changes of actin cytoskeleton organization in the process of cellular senescence, H-ras double mutants--V12S35, V12G37 and V12C40--proteins were expressed constitutively in human diploid fibroblast (HDF) cells by retrovirus infection at PD26 |
| 11080532 | Senescent HDF cells as well as the H-ras mutant expressers accumulated p-Erk1/2 in the cytoplasm with increased MEK activity and failed to translocate it to nuclei on EGF stimulation |
| 11080532 | In summary, the induced premature senescence by H-ras double mutants were accompanied by nuclear accumulation of actin and Racl proteins, cytoplasmic retention of p-Erk1/2 and marked induction of RhoA expression mainly through dysregulation of the MEK pathway |
| 9916803 | In addition, co-expression of telomerase, the viral oncoproteins HPV16 E6/E7 (which inactivate p53 and pRB) and oncogenic HRAS does not result in growth in soft agar |
| 8485202 | These cell lines were very useful inasmuch as a non-ras cellular transforming gene, met, and an activated H-ras oncogene have been isolated from MNNG-transformed and 3MC-transformed HOS lines, respectively, by DNA transfection procedure |
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