id string | sentence1 string | sentence2 string | score float64 |
|---|---|---|---|
78 | A recent study identified the importance of the GATA2 transcriptional network in RAS oncogene-driven NSCLC and suggested effective combinations targeting the proteasome together with IL-1 and Rho-signalling. | Alternatively, the anaphase promoting complex (APC) is responsible for the rapid degradation of cyclin D1 in cells irradiated with ionizing radiation. | 0.2 |
45 | In spite of these caveats, the results of research represent a very important advance in the long-standing fight to conquer lung cancer | We should consider the data of research as an exciting but early step in the long process of drug discovery. | 0.8 |
35 | Up-regulation of miR-24 has been observed in a number of cancers, including OSCC. | In addition, miR-24 is one of the most abundant miRNAs in cervical cancer cells, and is reportedly up-regulated in solid stomach cancers. | 3 |
50 | Further, INPP4B was identified out of a collection of RNAis to give rise to anchorage-independent growth in human mammary epithelial cells (HMEC) | On the other hand, RASA4/CAPRI (RAS p21 protein activator 4), a suppressor of epithelial cell transformation, functions as a Ca(2+)-dependent Ras GTPase-activating 0protein (GAP) to inactivate the Ras-MAPK pathway following a stimulus that elevates intracellular calcium | 0.6 |
27 | In many tumors, there is either overexpression of so-called oncogenic miRNAs (e.g., miR-155, miR-17−5p and miR-21) or downregulation of tumor suppressor miRNAs (e.g., miR-34, miR-15a, miR-16−1 and let-7) | Of note, miR-373 had been previously identified as a potential oncogene (together with miR-372) in testicular germ-cell tumors, although it has been proposed that the prometastatic and the oncogenic properties of this miRNA are due to the regulation of different genes (CD44 and LATS2, respectively) | 1.8 |
13 | Oct-4-dependent transcriptional networks have been described regulating self-renewal and pluripotency in human and mouse ES and EC cells and in human mesenchymal cells. | Co-transfection of miRVec-miR-204 and the Renilla-3′ UTR plasmid was in HEK293T cells with TransIT-LT1 Transfection Reagent (Mirus) | 0 |
87 | expression of an activated form of Ras proteins can induce senescence in some primary fibroblasts. | When expressed alone in primary cells however, oncogenic Ras induces premature senescence, a putative tumour suppressor mechanism to protect from uncontrolled proliferation. | 3 |
1 | Here, looking for agents that could specifically kill KRAS mutant cells, they found that knockdown of GATA2 was synthetically lethal with KRAS mutation | Not surprisingly, GATA2 knockdown in KRAS mutant cells resulted in a striking reduction of active GTP-bound RHO proteins, including the downstream ROCK kinase | 2.2 |
58 | Previous studies demonstrated that the decrease level of 5 hmC in tumors was due to the reduced expression of TET1/2/3 and IDH2 genes or tumor derived IDH1 and IDH2 mutations. | In addition, genetic and functional studies suggest that neomorphic IDH mutations contribute to myeloid transformation, at least in part, by inhibiting TET enzymatic function. | 2.2 |
99 | The researchers screened human NSCLC cell lines carrying either wild-type or mutant KRAS with an RNAi library against 7,000 human genes. | Recently, it was shown that Gata2 fulfills such role in mutant Kras induced NSCLC. | 1.8 |
55 | This oxidative branch activity is elevated in comparison to many cancer cell lines, where the oxidative branch is typically reduced and accounts for <20% of the carbon flow through PPP. | The Downward laboratory went all the way from identifying GATA2 as a novel synthetic lethal gene to validating it using Kras-driven GEM models. | 0 |
74 | With respect to LATS2, it has been reported that LATS2 induces G2/M arrest and subsequent apoptotic cell death. | The expression of miR-146a has been found to be up-regulated in papillary thyroid carcinoma, anaplastic thyroid cancer and cervical cancer. | 0.2 |
66 | Ironically, Rest has recently been described as both a tumor suppressor and an oncogene. | In human epithelial cells REST has been described as a potent suppressor of malignant transformation and its deregulation has been associated with several non-neural tumors including breast and small cell lung cancers | 3.2 |
39 | Recently, it was reported that expression of IDH1R132H suppresses TET2 activity and the mutations of IDH1 and IDH2 genes occur in a mutual exclusive manner with that of TET2 gene in AML. | This large-scale study showed that IDH1/IDH2 mutations were mutually exclusive with inactivating TET2 mutations, suggesting that the two types of mutations had similar effects and were thus functionally redundant. | 3.2 |
44 | Importantly, the role of ERK phosphorylation in Kras-driven NSCLCs has been recently highlighted by the demonstration that ERK activity is essential for Kras-driven lung tumorigenesis. | As mentioned above, high ERK activity is crucial for the development of Kras-driven NSCLCs. | 3.4 |
18 | The in vivo data is still preliminary and other potential roadblocks such as drug resistance have not been examined. | The GEM model used in this study retains wild-type Tp53, suggesting that the tumors successfully treated with bortezomib and fasudil might not be as aggressive as those in most NSCLC patients | 0 |
84 | Recently, miR-126 was identified as a metastasis suppressing miRNA that is downregulated in relapsing breast cancer, leukemia, and cervical cancer. | MiR-155 is upregulated in several human tumors, such as chronic lymphocytic leukemia, melanoma, head and neck squamous cell carcinoma, clear-cell kidney cancer , hepatocellular carcinoma, lymphoma, thyroid carcinoma], breast cancer, colon cancer, cervical cancer, pancreatic cancer, and lung cancer. | 2 |
76 | Consequently miRNAs have been demonstrated to act either as oncogenes (e.g., miR-155, miR-17−5p and miR-21) or tumor suppressors (e.g., miR-34, miR-15a, miR-16−1 and let-7) | The extent to which miRNAs specifically affect metastasis remains unclear, as all the miRNAs reported to affect metastasis also exert potentially confounding influences on primary tumor development, apoptosis, and/or cell proliferation | 2.8 |
19 | Recently, miR-126 was identified as a metastasis suppressing miRNA that is downregulated in relapsing breast cancer, leukemia, and cervical cancer. | Subsequent reports showed that miR-126 targeted the oncogene IRS-1 (insulin receptor substrate-1) in breast cancer cells and miR-126 was downregulated in cervical cancer. | 3.2 |
10 | The recent reports demonstrated that the first eight nucleotides of the 5′ end of miRNA could correlate with the efficient translational repression. | Mismatches near the 5′ end of the small RNA completely abrogated translational suppression. | 3.2 |
75 | Considerable evidence indicates that cancer cells develop dependencies on normal functions of certain genes that can potentially be exploited to improve therapeutic strategies. | In the case of cell response to stress, cyclin D1 can be degraded through its binding to the anaphase-promoting complex and a RXXL sequence located in the NH2-terminal part of the protein. | 0 |
46 | The mammalian Arp, BAF53 (BRG-associated factor), and β-actin were initially found as components of the mammalian SWI/SNF-like BAF chromatin-remodeling complex. | In addition, Arp4-related BAF53 and β-actin are components of the human SWI/SNF complex and could play a role in its signal-regulated binding to the chromatin/nuclear matrix | 3.4 |
15 | A gene that warrants further studies is the erythropoietin receptor that is 7.4-fold higher expressed in TEL-AML1-positive cases compared to other precursor B-ALL cases confirming other gene expression classification studies. | Another recent gene expression study of large numbers of cases provided support for the hypothesis that distinct leukemias are specified by each of the unique chromosomal abnormalities found in lymphoblastic leukemias. | 0.6 |
86 | Third, human Wts2 is a phosphorylation target of Aurora-A kinase, and this phosphorylation plays a role in regulating centrosomal localization of hWts2 ( Toji et al., 2004) | Similarly to PLK1, Aurora-A activity is required for the enrichment or localisation of multiple centrosomal factors which have roles in maturation, including LATS2 [ 22] and CDK5RAP2/Cnn [ 23] (see [ 10] for a review) | 1.2 |
60 | Three programs, PicTar, miRanda, and TargetScan , were used to predict the targets of miR-21. | The genes that decreased 2-fold or more were further screened for possible miR-372/3 target sites using a local version of the TargetScan algorithm. | 2.4 |
14 | In eukaryotic cells, small G-proteins are critically regulated by Guanine nucleotide Exchange Factors (GEFs) and GTPase Activating Proteins (GAPs). | Eukaryotic small G-proteins are often controlled through the balancing actions of GAPs and GEFs. | 4 |
51 | The overall accuracy of our gene expression classifier was ~88%, and all T-ALL, TEL-AML1-positive, hyperdiploid and E2A-rearranged cases were correctly classified (i.e., 100% sensitivity) which resembled the data previously reported using other strategies for probe set selection and classifier construction. | A gene that warrants further studies is the erythropoietin receptor that is 7.4-fold higher expressed in TEL-AML1-positive cases compared to other precursor B-ALL cases confirming other gene expression classification studies. | 2 |
79 | Alterations in Oct-4 expression promote differentiation and leads to the specification of ectodermal, endodermal or mesodermal primitive progenitors. | OCT4, a transcript of POU5F1, plays a role in maintaining stem cell pluripotency, self-renewal and chromatin structure in stem cells, and promotes tumor growth in a dose-dependent manner. | 1.6 |
29 | This form of necrosis, also termed necroptosis, requires the activity of receptor-interacting protein kinase 1 (RIP1) and its related kinase, RIP3 | TNF-mediated programmed necrosis typically involves the receptor-interacting serine-threonine kinases 1 and 3 (RIP1 and RIP3), as evidenced in human, mouse, and zebrafish cell lines, as well as in a murine sepsis model | 3 |
34 | We, and others, have recently described the inducible-Kras*p53+/− (iKras*p53+/−) mouse model of pancreatic cancer, that allows tissue-specific, inducible and reversible expression of mutant Kras in combination with a loss of function allele of the tumor suppressor p53. | There is a certain variability in these findings: for instance, metastatic potential has been described by other groups using KC or iKras* mice combined with loss of function allele of p53. | 3 |
94 | miR-223 regulates granulopoiesis by a feedback mechanism and is modulated competitively by the transcription factors nuclear factor I/A (NFI-A) and CCAAT/enhancer binding protein-α (C/EBPα) | There is growing evidence from animal systems that miRNA-regulated transcription factors frequently regulate the transcription of their cognate miRNAs. | 1.8 |
28 | In lung tumors, TRAF6 levels can become elevated by several mechanisms: | GATA2lox/lox Sporadic infection of lung cells with Adeno-Cre virus GATA2 loss induces regression of established tumors | 1.4 |
62 | More recently, IDH mutations and resultant 2-hydroxyglutarate (2HG) production in leukemia cells were reported to induce global DNA hypermethylation through impaired TET2 catalytic function. | It has also been recently reported that mutations of the isocitrate dehydrogenase genes IDH1 and IDH2 can lead to the aberrant production of 2-hydroxyglutarate (2-HG), a metabolite that inhibits TET2 enzymatic activity, resulting in a hypermethylated promoter phenotype in acute myeloid leukemia (AML) tumors carrying ID... | 3.2 |
42 | For Sox11 repression by miR-204, Neuro-2a cells (ATCC) were grown on coverslips in 24-well plates for 24 h and then co-transfected with 500 ng of pCAG-GFP expression plasmid and either 500 ng of scrambled-miRVec or miR-204-miRVec expression plasmid containing the pre-miRNA of miR-204 | Co-transfection of miRVec-miR-204 and the Renilla-3′ UTR plasmid was in HEK293T cells with TransIT-LT1 Transfection Reagent (Mirus) | 1.8 |
21 | They identified that some genes involved in RHO-related signaling pathways were occupied by GATA2 in KRAS mutant but not wild-type tumor cells. | The researchers combined available inhibitors selective for two of the pathways regulated by GATA2 to treat mice with Kras-driven NSCLCs | 2 |
30 | The oncogenic activity of mutant Kras appears dependent on functional Craf, but not on Braf | Notably, c-Raf has recently been found essential for development of K-Ras-driven NSCLCs | 3 |
11 | Ironically, Rest has recently been described as both a tumor suppressor and an oncogene. | REST is a transcription factor that represses neuronal genes in non-neural tissues, and plays a prominent tumor suppressor role in epithelial tissues | 3 |
53 | Several lines of evidence suggest that the known principal RB pathway lesions in human tumors act in a mutual exclusive manner. | In individual human tumor specimens, these principal components of the pathway—RB-CDK4/6-p16INK4A—are reported to be targeted in a mutually exclusive manner. | 3.4 |
6 | Furthermore, transiently expressed exogenous LATS2 is localized to centrosomes. | LATS1 and LATS2 have been detected on interphase and mitotic centrosomes | 3 |
12 | Finally, researchers combined available inhibitors selective for two of the pathways regulated by GATA2 to treat mice with Kras-driven NSCLCs. | In PC9 cells, loss of GATA6 and/or HOPX did not alter cell growth, whereas reduction of GATA2 and EGFR inhibited cell viability as previously reported. | 1.8 |
26 | Since in S. cerevisiae DBF2 was shown to be associated with anaphase and/or telophase progression, we examined whether the deletion of the kinase would also affect cell cycle progression in N. crassa | Taking into consideration the role that DBF2 homologs have been shown to play in cell cycle progression, predominant localization of DBF-2 in N.crassa is expected. | 2 |
48 | Oct-4-dependent transcriptional networks have been described regulating self-renewal and pluripotency in human and mouse ES and EC cells and in human mesenchymal cells. | One study reports upregulation of this miR as revealed by qRT-PCR whereas a sequencing approach and microarray analysis point to a repression of miR-133b in tumor tissue | 0.6 |
31 | The up-regulation of miR-146a was also detected in cervical cancer tissues. | The expression of miR-146a has been found to be up-regulated in cervical cancer. | 4 |
32 | Unique segments of homologous sequences in RIP1 and RIP3 (RIP homotypic interaction motifs, RHIMs) were shown to mediate their interaction | RIP1 was reported to interact with RIP3. | 3.4 |
77 | Recently, it was reported that expression of IDH1R132H suppresses TET2 activity and the mutations of IDH1 and IDH2 genes occur in a mutual exclusive manner with that of TET2 gene in AML | the mechanism was clarified by yet another genomic survey, this time involving acute myelogenous leukemia (AML). | 1.6 |
37 | The phenomena of neoplastic development and neoplastic transformation, whether they occur in vivo or in vitro, are thought to represent the accumulation of a series of genetic and epigenetic alterations that disrupt the normal processes of cell division and tissue integrity. | Neoplastic development represents cumulative genetic and epigenetic events leading to the emergence of cells that can attain a tumorigenic phenotype. | 3 |
95 | Importantly, RNAi knockdown of Gfpt1 reduced overall O-GlcNAcylation and blocked KrasG12DA-mediated tumor growth in vitro and in vivo. | GFPT1 is the rate-limiting enzyme in the HBP and it has been identified as an important contributor to Kras-driven pancreatic ductal adenocarcinoma (PDAC) | 2.2 |
85 | Centrosomes increase both in size and in microtubule-nucleating capacity just before mitotic entry. | Functional studies showed that, when introduced into cell lines, miR-146a was found to promote cell proliferation in cervical cancer cells, which suggests that miR-146a works as an oncogenic miRNA in these cancers. | 0 |
36 | This form of necrosis, also termed necroptosis, requires the activity of receptor-interacting protein kinase 1 (RIP1) and its related kinase, RIP3 | Moreover, other reports have also shown that necroptosis could be induced via modulating RIP1 and RIP3. | 4 |
56 | Activated Ras will transform established lines, such as NIH3T3 cells, it causes a senescence-like growth arrest in primary cells | Moreover, oncogenes such as H-RASV12 provoke a stress response in primary cells that results in an irreversible growth arrest, termed premature senescence. | 3 |
43 | Furthermore, ablation of both Erk1 and Erk2 impaired tumor development, whereas inactivation of either one alone had no effect. | Only concomitant ablation of ERK1 and ERK2 impairs tumor growth. | 4 |
61 | The Retinoblastoma protein, pRb, was among the first recognized tumor suppressor proteins, and loss or repression of pRb function is thought to play a causative role in most human cancers. | Mutation of the retinoblastoma tumor susceptibility gene (RB1) is the rate-limiting step in the genesis of retinoblastoma and over 90% of human tumors exhibit reduced pRB function. | 3 |
16 | For example, loss of, or functional alterations in, the two major tumor suppressor proteins pRB and p53 cause an up-regulation of ribosome biogenesis in cancer tissues. | E2F1 stabilizes p53 by inducing the expression of p19(p14)/ARF, an inhibitor of the mdm2 ubiquitin ligase that targets p53 for proteolysis. | 2 |
5 | We then sought to reassess the regulation of miR-223 in the exactly same experimental system adopted in the previous work | Importantly, our reassessment revealed that this conserved promoter is probably active in the induction of miR-223 during All-trans retinoic acid (ATRA)-induced differentiation of the APL cell line, NB4 cells, which is the main experimental system adopted in the previous study | 2.4 |
67 | In PC9 cells, loss of GATA6 and/or HOPX did not alter cell growth whereas reduction of GATA2 and EGFR inhibited cell viability as previously reported. | It has been shown that the activities of many regulatory factors of checkpoints are lost or arrested during the process of tumorigenesis. | 0.2 |
65 | It has been shown, however, that ubiquitination of cyclin D1 can efficiently take place following phosphorylation of another site, or without the apparent requirement for phosphorylation. | APC-dependent degradation of cyclin D1 does not require threonine 286 phosphorylation, but the presence of a “cyclin degradation box”, however, as observed in the present study, threonine 286 phosphorylation is essential for proteolytic degradation of cyclin D1 in skin | 3 |
54 | Recent in vitro studies using shRNA-based approaches have suggested a role for TET2 in regulating myeloid differentiation and in regulating stem/progenitor cell proliferation. | Two recent studies used RNAi-mediated Tet2 knock-down in vitro to suggest that TET2 depletion led to impaired hematopoietic differentiation and to preferential myeloid commitment. | 3.2 |
3 | The oncogenic activity of mutant Kras appears dependent on functional Craf. | Oncogenic KRAS mutations are common in cancer. | 2 |
73 | Lung tumour formation in mice by oncogenic KRAS requires CRaf, but not BRaf. | The oncogenic activity of mutant Kras appears dependent on functional Craf but not on Braf. | 3.4 |
98 | A high percentage of tumor cells that take on immortalized characteristics show telomerase activity and it has been suggested that hTERT expression may be one of the six key events common to cancer. | As a serine/threonine protein kinase, AKT functions by phosphorylating key intermediate signaling molecules, leading to increased cell metabolism, cell growth, cell survival, and cell invasiveness—all hallmarks of cancer. | 1.4 |
17 | We found no obvious effect of LATS2-depletion on the Aurora-A kinase activity when monitored by phosphorylation state of Thr288 on Aurora-A [18] (Fig. S2), suggesting that LATS2 may be a downstream of Aurora-A as mentioned in a previous report [8] | Among them, miR-143, miR-145 and miR-34a have been shown to inhibit cell proliferation, and miR-146a and miR-21 to increase cell growth | 0.2 |
4 | Consequently miRNAs have been demonstrated to act either as oncogenes (e.g., miR-155, miR-17−5p and miR-21) or tumor suppressors (e.g., miR-34, miR-15a, miR-16−1 and let-7) | Given the extensive involvement of miRNA in physiology, dysregulation of miRNA expression can be associated with cancer pathobiology including oncogenesis], proliferation, epithelial-mesenchymal transition, metastasis, aberrations in metabolism, and angiogenesis, among others | 2.8 |
92 | The up-regulation of miR-146a was also detected in cervical cancer tissues. | Similarly to PLK1, Aurora-A activity is required for the enrichment or localisation of multiple centrosomal factors which have roles in maturation, including LATS2 and CDK5RAP2/Cnn. | 0.2 |
93 | Oncogenic KRAS mutations are common in cancer. | Notably, c-Raf has recently been found essential for development of K-Ras-driven NSCLCs. | 1.8 |
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