Abstract:
:Doublecortin-like kinase 1 (DCLK1) is a cancer stem cell marker for the colorectal cancer (CRC). It plays critical roles in the oncogenesis, progression, and metastasis of CRC. DCLK1 can be an intriguing therapeutic target for CRC treatment. However, the molecular mechanism of how DCLK1 functions is unclear currently. In our research, we aim to apply RNA-Sequencing (RNA-Seq) technology, a high throughput massively Next-generation sequencing approach, to monitor transcriptome changes due to DCLK1 overexpression in the CRC cells. In order to achieve our goal, RNA from quadruplicate samples from two clones of isogenic DCLK1 stable overexpression cells and the parental wild-type HCT116 cells was sent for RNA-Seq on the Illumina NextSeq500 platform. Differentially expressed (DE) genes were evaluated by t-test (P < 0.05 and fold-change ± 1.5 or greater) using two methods: (1) FWER; and (2) Benjamani and Hochberg FDR (false discovery rate) which corrects for multiple comparisons. Gene networks and functional analysis were evaluated using Ingenuity Pathways Analysis (IPA). We identified 1463 DE genes common for both DCLK1 overexpression clone A and clone B cells. IPA results indicated that 72 canonical pathways were significantly modified by DCLK1 overexpression (P < 0.05), among which nine out of the top ten pathways are involved in the cell cycle regulation, indicating that DCLK1 might play its tumorigenesis role via activation of pathways facilitating cell proliferation, repression of pathways inhibiting cells proliferation, and function against pathways facilitating cell apoptosis. Cell cycle analysis results confirmed the IPA findings, which demonstrated that DCLK1 overexpression cells had much less G0/G1 cells but much more S and G2/M cells (P < 0.05). In conclusion, DCLK1 overexpression significantly modified transcriptome profile of CRC cancer cells. Control of the cell cycle regulation might be one of the critical mechanism for DCLK1 function. Our findings provide more direct evidence for the development of DCLK1 as a therapeutic target for CRC treatment, and will be of great benefit for the discovery of novel therapeutic target within the DCLK1 molecular network for the treatment of colorectal cancer patients.
journal_name
Cancer Gene Therjournal_title
Cancer gene therapyauthors
Li L,Mei H,Commey ANAdoi
10.1038/s41417-019-0144-4subject
Has Abstractpub_date
2020-09-01 00:00:00pages
691-701issue
9eissn
0929-1903issn
1476-5500pii
10.1038/s41417-019-0144-4journal_volume
27pub_type
杂志文章abstract::Due to the lack of early diagnostic and effective treatment modalities, hepatocellular carcinoma (HCC) is still the most lethal cancer with a high mortality on a global scale. Recent studies have highlighted the key roles of microRNAs (miRs) in HCC development. In the study, we attempted to investigate the potential r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00253-w
更新日期:2020-11-30 00:00:00
abstract::Herpes simplex viruses (HSVs) are important pathogens and ideal for gene therapy due to its large genome size. Previous researches on HSVs were hampered because the technology to construct recombinant HSVs were based on DNA homology-dependent repair (HDR) and plaque assay, which are inefficient, laborious, and time-co...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/s41417-018-0016-3
更新日期:2018-06-01 00:00:00
abstract::Treatment of metastatic tumors with engineered adenoviruses that replicate selectively in tumor cells is a new therapeutic approach in cancer. Systemic administration of these oncolytic adenoviruses lack metastatic targeting ability. The tumor stroma engrafting property of intravenously injected mesenchymal stem cells...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2010.4
更新日期:2010-07-01 00:00:00
abstract::Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2008.31
更新日期:2008-12-01 00:00:00
abstract::Recurrent or metastatic cancer in most cases remains an incurable disease, and thus alternative treatment strategies, such as oncolytic virotherapy, are of great interest for clinical application. Oncolytic adenoviruses (Ads) have many advantages as virotherapeutic agents and have been safely employed in the clinics. ...
journal_title:Cancer gene therapy
pub_type: 杂志文章,评审
doi:10.1038/cgt.2012.95
更新日期:2013-02-01 00:00:00
abstract::Sodium iodide symporter (NIS) reporter gene imaging is an excellent technology for noninvasive cell fate determination in living animals unless the NIS-transduced cells reside in perigastric organs such as the spleen, liver, diaphragm, omentum, pancreas, perigastric lymph nodes or perigastric tumor deposits. Here we r...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2013.57
更新日期:2013-11-01 00:00:00
abstract::Targeting tumor vasculature represents an interesting approach for the treatment of solid tumors. The alpha v beta 3 integrins have been found to be specifically associated with angiogenesis in tumors. By using bacteriophage display technology, Ruoslahti et al found that a group of peptides containing the RGD (Arg-Gly...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700707
更新日期:2004-05-01 00:00:00
abstract::Lung cancer is the most frequently occurring cancer in the world and causes more deaths in the United States than does colon, breast, and prostate cancer combined. Despite advances in treatment modalities including radiation, surgery, and chemotherapy, the overall survival in lung cancer remains low. The cytokine tumo...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700394
更新日期:2001-11-01 00:00:00
abstract::Mortality due to colorectal cancer (CRC) is high and is associated with the development of liver metastases. Approximately 40% of human CRCs harbor an activating mutation in the KRAS oncogene. Tumor cells with activated KRAS are particularly sensitive to Reovirus T3D, a non-pathogenic oncolytic virus. The efficacy of ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700949
更新日期:2006-08-01 00:00:00
abstract::Apoptotic pathways are initiated as a cellular defense mechanism to eliminate adenovirus-infected cells. We have investigated how E1A-induced apoptosis interferes with viral replication in cancer cells. We found that E1B19K alone can efficiently suppress E1A-induced apoptosis in cancer cells. Viruses deleted for both ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700739
更新日期:2004-09-01 00:00:00
abstract::To develop novel therapies for aggressive thyroid cancers, we have synthesized a collection of histone deacetylase (HDAC) inhibitor analogs named AB1 to AB13, which have different linkers between a metal chelating group and a hydrophobic cap. The purpose of this study was to screen out the most effective compounds and...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2015.37
更新日期:2015-08-01 00:00:00
abstract::The Holliday Junction-Recognition Protein (HJURP) was reported as overexpressed in several cancers and also strongly correlated with poor prognosis of patients, especially in glioblastoma (GBM), the most common and deadly type of primary brain tumor. HJURP is responsible for loading the histone H3 variant-the Centrome...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0103-0
更新日期:2020-05-01 00:00:00
abstract::To identify the differentially expressed genes (DEGs) and their transcription factors (TFs) in colorectal cancer (CRC). We performed an integrated analysis of microarray studies. Functional annotation and CRC-specific transcriptional regulatory network construction were performed. Expression of selected DEGs and TFs w...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2017.8
更新日期:2017-06-01 00:00:00
abstract::The highly metastatic ESb tumor is totally resistant to murine interferon-alpha/beta (IFN-alpha/beta) therapy, regardless of the number of cells injected or the route of inoculation. In contrast, as we show herein, mouse IFN-alpha1-transduced ESb tumor cells were inhibited markedly when injected subcutaneously into im...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700051
更新日期:1999-05-01 00:00:00
abstract::Oncolytic virotherapy has shown substantial promises as an alternative therapeutic modality for solid tumors in both preclinical studies and clinical trials. The main therapeutic activity of virotherapy derives from the direct lytic effect associated with virus replication and the induction of host immune responses to...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2011.46
更新日期:2011-11-01 00:00:00
abstract::The present study was designed to investigate the upstream transcription factors (TFs) and the signature genes in cholangiocarcinoma (CCA), providing better clues on the regulatory mechanisms and therapeutic applications. Gene expression data sets of CCA were searched in the Gene Expression Omnibus database for integr...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2016.64
更新日期:2016-12-01 00:00:00
abstract::Transfer of genes to the gastrointestinal epithelium would be advantageous from investigational and therapeutic standpoints. Efficient transfer of DNA to the intestinal epithelial cells, however, has been problematic with conventional viral and nonviral vectors. As an alternative, we have utilized molecular conjugate ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Replication-selective oncolytic viruses are being developed for human cancer therapy. We previously developed an attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1A and E1B genes linked with an internal ribosome entry site. OBP-301...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/cgt.2012.57
更新日期:2012-11-01 00:00:00
abstract::We examined whether novel cytokines, interleukin (IL)-21 and IL-23, that were expressed in tumors could produce antitumor effects in the inoculated mice. Human pancreatic cancer AsPC-1 cells were retrovirally transduced with murine IL-21 or IL-23 (p19-linked p40) gene (AsPC-1/IL-21, AsPC-1/IL-23) and were injected int...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700630
更新日期:2003-10-01 00:00:00
abstract::The use of genetically modified tumor cells as vaccines has been successful in numerous animal models of grafted syngenic tumors and has provided the groundwork for many clinical trials of gene therapy in cancer patients. To investigate the real efficacy of ex vivo gene therapy-based vaccines, we used transgenic mice ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
abstract::The herpes simplex virus thymidine kinase (HSV-TK) gene is being developed in the treatment of many different types of tumors. The HSV-TK gene sensitizes tumor cells to the antiviral drug ganciclovir (GCV) and mediates the bystander effect in which unmodified tumor cells are killed as well. Although this approach has ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700063
更新日期:1999-09-01 00:00:00
abstract::Chimeric antigen receptor (CAR) therapy has shown promise against B cell malignancies in the clinic. However, limited success in patients with solid tumors has prompted the development of new CAR strategies. In this study, a B7H6-specific CAR was combined with different variants of T-bet, a transcription factor that a...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-018-0012-7
更新日期:2018-06-01 00:00:00
abstract::A recombinant adenovirus expressing Escherichia coli cytosine deaminase (AdCD) was constructed with the purpose of exploring its utility for the treatment of breast cancer. Infection of the human breast cancer cell line, MDA-MB-231, with AdCD resulted in high levels of cytosine deaminase enzyme activity. MDA-MB-231 ce...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Chimeric Antigen Receptor (CAR) T-cell therapy, as an approved treatment option for patients with B cell malignancies, demonstrates that genetic modification of autologous immune cells is an effective anti-cancer regimen. Erythropoietin-producing Hepatocellular receptor tyrosine kinase class A2 (EphA2) is a tumour ass...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00221-4
更新日期:2020-09-01 00:00:00
abstract::Although gene therapies using tissue-specific promoters have been reported to be a promising tool for treating cancers, few studies have explored this possibility for uterine cervical cancer. MN/CA9 is a transmembrane glycoprotein that was first identified in the human cervical carcinoma cell line, HeLa. Since MN/CA9 ...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700732
更新日期:2004-08-01 00:00:00
abstract::Using our model to grow superficial human bladder cancer in the mouse bladder, we have found that the polyamide compound, Syn3, when injected intravesically for 1 hour at 1 mg/mL on two consecutive days, markedly increases rAd-beta-gal intravesical gene transfer and expression. This enhanced transgene expression was m...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700488
更新日期:2002-08-01 00:00:00
abstract::Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death worldwide. Accumulating research has highlighted the ability of exosome-encapsulated microRNAs (miRNAs or miRs) as potential circulating biomarkers for lung cancer. The current study aimed to evaluate the clinical significance of seru...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-020-00216-1
更新日期:2020-12-09 00:00:00
abstract::Prostate cancer is the second most common cancer in men globally. Prostate cancer patients at advanced stages are usually treated with androgen deprivation therapy (ADT). However, with disease progression, it often becomes the incurable castration-resistant prostate cancer (CRPC). JC polyomavirus (JCPyV) is a human DN...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/s41417-019-0083-0
更新日期:2019-07-01 00:00:00
abstract::p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was c...
journal_title:Cancer gene therapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1038/sj.cgt.7700214
更新日期:2000-07-01 00:00:00
abstract::The use of prodrug-activated ("suicide") gene therapy has been shown to be effective in inducing tumor regression when only a small proportion of tumor cells contains the suicide gene. These experiments were designed to test whether additional therapeutic benefit may be obtained by stimulating the immune response. Mur...
journal_title:Cancer gene therapy
pub_type: 杂志文章
doi:10.1038/sj.cgt.7700259
更新日期:2000-12-01 00:00:00