Abstract：
:DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored. Here, aberrant DIS3L2 expression promoted human hepatocellular carcinoma (HCC) progression via heterogeneous nuclear ribonucleoproteins (hnRNP) U-mediated alternative splicing. DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1 independent of its exonuclease activity, yielding an oncogenic splicing variant, Rac1b, which is known to stimulate cellular transformation and tumorigenesis. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Rac1b was critical for DIS3L2 promotion of liver cancer development both in vitro and in vivo. Importantly, DIS3L2 and Rac1b expression highly correlated with HCC progression and patient survival. Taken together, our findings uncover an oncogenic role of DIS3L2, in which it promotes liver cancer progression through a previously unappreciated mechanism of regulating hnRNP U-mediated alterative splicing. SIGNIFICANCE: These findings establish the role and mechanism of the 3'-5' exoribonuclease DIS3L2 in hepatocellular carcinoma carcinogenesis.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Xing S,Li Z,Ma W,He X,Shen S,Wei H,Li ST,Shu Y,Sun L,Zhong X,Huangfu Y,Su L,Feng J,Zhang X,Gao P,Jia WD,Zhang Hdoi
10.1158/0008-5472.CAN-19-0376subject
Has Abstractpub_date
2019-10-01 00:00:00pages
4923-4936issue
19eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-19-0376journal_volume
79pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:10-Ethyl-10-deazaaminopterin (10-EdAM) is an antifolate compound with greater therapeutic activity than methotrexate against transplanted tumors in mice. When given weekly for 3 weeks, the 10% lethal dose in rats was 125 mg/kg (i.p.) and in dogs it was 2.5 mg/kg (i.v.). The major histopathological findings in intoxica...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-05-01 00:00:00
abstract：:The aim of this study is to explore the mechanisms of intratumoral cytogenetic heterogeneity (ICH) in pancreatic cancer. Using comparative genomic hybridization (CGH) analysis, we investigated interglandular variation in 20 primary invasive ductal adenocarcinomas of the pancreas. Three or four adjacent neoplastic glan...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-02-01 00:00:00
abstract：:3,4-Dihydro-2,2-dimethyl-2H-naptho[1,2,-b]pyran-5,6-dione (beta-lapachone) is a novel DNA repair inhibitor. It was tested for synergistic X-ray-induced lethality in combination with several halogenated pyrimidine radiosensitizers. Logarithmic-phase growing human epidermoid laryngeal carcinoma (HEp-2) cells were allowe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1987-10-15 00:00:00
abstract：:Anchorage-independent growth is a hallmark of tumor cells. We compared gene expression profiles of anchored and nonanchored human mammary carcinoma cells to study this phenomenon. In this study, we show that anchorage had striking effects on cell growth and morphology but altered transcript levels from a limited numbe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-02-15 00:00:00
abstract：:Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-3332
更新日期：2016-05-15 00:00:00
abstract：:Batracylin (8-aminoisoindolo [1,2-b]quinazolin-10(12H)-one; NSC320846) is an investigational clinical anticancer agent. Previous animal studies showed activity against solid tumors and Adriamycin-resistant leukemia. We initially sought to test the proposed Top2-mediated DNA cleavage activity of batracylin and identify...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-0804
更新日期：2007-10-15 00:00:00
abstract：:Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine metabolism. Targeting arginine metabolism, either by blocking cationic amino acid transporter 1 (CA...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-2139
更新日期：2019-02-01 00:00:00
abstract：:We have used high-pressure liquid chromatography and the Salmonella/microsome mutagenicity test to look for mutagenic impurities in 11 carcinogens and noncarcinogens. Because of the million-fold range in mutagenic potency observed in the Salmonella test, even trace amounts of potent mutagenic impurities in a nonmutage...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1978-02-01 00:00:00
abstract：:Despite the apparent similarity of the dexamethasone-receptor concentration in the rat liver and Novikoff hepatoma cytoplasms, the in vitro translocation of the dexamethasone-receptor complex into liver or hepatoma nuclei was three times greater from liver as compared to hepatoma cytosol; both cytosols showed an appar...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-06-01 00:00:00
abstract：:Resistance to antineoplastic drugs is a major problem in the clinical management of cancer. Previous studies have demonstrated that the cytotoxicity of certain anticancer drugs is increased by lowering the glutathione (GSH) levels with buthionine sulfoximine (BSO), a specific inhibitor of gamma-glutamylcysteine synthe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:The presence of common genomic deletions in the 19q13 chromosomal region in neuroblastomas and gliomas strongly suggests the presence of a putative tumor suppressor gene for these neoplasms in this region that, despite much effort, has not yet been identified. In an attempt to address this issue, we compared the expre...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-4283
更新日期：2005-04-01 00:00:00
abstract：:Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as basigin or CD147, is a glycoprotein that is enriched on the surface of tumor cells and stimulates production of several matrix metalloproteinases by adjacent stromal cells. In this study, we have found that EMMPRIN not only stimulates the producti...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-02-15 00:00:00
abstract：:The human checkpoint kinase 2 (Chk2) plays a central role in regulation of the cellular response to DNA damage, resulting in cell cycle arrest, DNA repair, or apoptosis depending on severity of DNA damage and the cellular context. Chk2 inhibitors are being developed as sensitizers for chemotherapeutic agents. In contr...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0677
更新日期：2005-07-15 00:00:00
abstract：:Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1976-07-01 00:00:00
abstract：:N4G3, a cell line that overexpresses translation initiation factor eIF4G, one of the components of eIF4F, was made by stable transfection of the human eIF4G cDNA into NIH3T3 cells. The cells expressed 80-100 times greater levels of eIF4G mRNA than did NIH3T3 cells. N4G3 cells formed transformed foci on a monolayer of ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-11-15 00:00:00
abstract：:The purpose of the present study was to define the immunogenicity of two transplantable rat gliomas, designated F98 and D74, and to relate this to the phenotype and functional activity of tumor-infiltrating lymphocytes (TIL). Fischer rats, immunized with irradiated F98 tumor cells and challenged with intracerebral imp...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Checkpoint pathways help cells maintain genomic integrity, delaying cell cycle progression in response to various risks of fidelity, such as genotoxic stresses, compromised DNA replication, and impaired spindle control. Cancer cells frequently exhibit genomic instability, and recent studies showed that checkpoint path...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-3927
更新日期：2007-02-01 00:00:00
abstract：:Recent studies have proposed that tumor necrosis factor alpha (TNF-alpha) and ionizing radiation induce apoptosis by activating hydrolysis of sphingomyelin to ceramide. Bcl-2 and a related gene, Bcl-X, inhibit several forms of apoptosis. Herein, we report that internucleosomal DNA fragmentation, characteristic of apop...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Multiple myeloma is a B-cell malignancy for which no curative therapies exist to date, despite enormous research efforts. The remarkable activity of the proteasome inhibitor bortezomib (PS-341, Velcade) observed in clinical trials of patients with relapsed refractory myeloma has led to investigations of the role of th...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0506
更新日期：2005-09-01 00:00:00
abstract：:Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series of 20 sporadic breast carcinomas and corresponding blood samples...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:The high mortality of pancreatic cancer demands that new therapeutic avenues be developed. The orally available small-molecule inhibitor AT13148 potently inhibits ROCK1 and ROCK2 kinases that regulate the actomyosin cytoskeleton. We previously reported that ROCK kinase expression increases with human and mouse pancrea...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1339
更新日期：2018-06-15 00:00:00
abstract：:Many but not all of the cell surface antigens studied were released into tissue culture medium of human colorectal carcinoma and melanoma cells maintained in vitro. Two groups of monoclonal antibody-defined antigens are described. One group is composed of molecules that are released easily and in large quantitites int...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-07-01 00:00:00
abstract：:Radioimmunoassay has been used to measure acetylated and deacetylated deoxyguanosine C-8 DNA adducts of 2-acetylaminofluorene in liver and kidney DNA of male Wistar-Furth rats fed a dietary regimen of 0.02 or 0.04% 2-acetylaminofluorene. When adduct formation was monitored during continuous feeding up to 60 days, subs...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-04-01 00:00:00
abstract：:Gene-targeting studies have shown that Delta-like 4 (Dll4) is required for normal embryonic vascular remodeling, but the mechanisms underlying Dll4 regulatory functions are not well defined. We generated primary human umbilical vascular endothelial cells that express Dll4 protein to study Dll4 function and previously ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-2181
更新日期：2008-03-15 00:00:00
abstract：:Genetic instability, a hallmark feature of human cancers including prostatic adenocarcinomas, is considered a driver of metastasis. Somatic copy number alterations (CNA) are found in most aggressive primary human prostate cancers, and the overall number of such changes is increased in metastases. Chromosome 10q23 dele...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3280
更新日期：2016-01-15 00:00:00
abstract：:We tried to purify carcinoembryonic antigen (CEA)-related antigens in normal human feces and found that, besides nonspecific cross-reacting antigen (fecal NCA), there are three other molecular species of CEA-related antigens which have been inclusively called normal fecal antigen (NFA). These were designated normal fe...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-02-01 00:00:00
abstract：:We used somatic cell hybridization to determine whether the regressor phenotype exhibited by UV-induced murine tumors was dominant or recessive and whether this technique could confer immunogenic properties on nonimmunogenic syngeneic tumors. We transfected a highly antigenic UV-induced C3H mouse tumor cell line (UV-2...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-03-01 00:00:00
abstract：:Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-12-01 00:00:00
abstract：:The increasing availability and maturity of DNA microarray technology has led to an explosion of cancer profiling studies. To extract maximum value from the accumulating mass of publicly available cancer gene expression data, methods are needed to evaluate, integrate, and intervalidate multiple datasets. Here we demon...
journal_title：Cancer research
pub_type： 杂志文章,meta分析
doi：
更新日期：2002-08-01 00:00:00
abstract：:In acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA) treatment induces granulocytic maturation and complete remission of leukemia. microRNAs are known to be critical players in the formation of the leukemic phenotype. In this study, we report downregulation of the miR-181a/b gene cluster in APL blasts...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-14-3521
更新日期：2015-08-15 00:00:00
