Abstract:
BACKGROUND:HOX transcript antisense RNA (HOTAIR), which is expressed from the homebox C gene (HOXC) locus, is capable of reprogramming chromatin organisation and promoting cancer cell metastasis and can simultaneously bind the polycomb repressive complex 2, which enhances H3K27 trimethylation, and the LSD1-CoREST-REST complex, which is critical for H3K4 demethylation. Clinically, the overexpression of HOTAIR is a powerful predictor of the tumour progression and overall survival in patients with diverse cancers. The relationship between HOTAIR and oesophageal squamous cell carcinoma (ESCC), however, remains unclear. We investigated the role of HOTAIR in the pathogenesis of ESCC. METHODS:We used quantitative real-time PCR to determine the level of HOTAIR in ESCC cell lines and 100 ESCC samples from patients; 56 adjacent non-neoplastic tissues were used as controls. We measured the effect of HOTAIR knockdown and overexpression in ESCC cell lines using colony formation assays, anchorage-independent growth assays, the CCK-8 assay, transwell migration and invasion assays, and Annexin V-binding assays. We analysed the growth of ESCC xenograft tumours in nude mice. Changes in the gene expression and methylation levels in ESCC cell lines were analysed using gene expression microarrays and the Infinium HumanMethylation450K BeadChip assay, respectively. results: The levels of HOTAIR were increased in ESCC cell lines and patient samples compared with the controls; the expression levels correlated with the disease stage and survival time. The knockdown of HOTAIR in the KYSE510 and KYSE180 ESCC cell lines using small hairpin RNAs (shRNAs) reduced the ability of the cells to form foci, migrate, and invade the extracellular matrix in culture, altered cell cycle progression, and increased the sensitivity of the cells to apoptosis. The HOTAIR knockdown reduced cancer cell metastasis in vivo, and the tumours formed by HOTAIR-silenced ESCC cells were smaller, both in size and weight, than the tumours and metastases formed by the shRNA vector control cells in a mouse xenograft model. The results of the gene microarray study showed that HOTAIR reprogrammed the gene expression profile of ESCC cells, and the gene ontology analysis revealed an enrichment in genes that are important for tumorigenesis, such as genes involved in cell migration and the regulation of the cell cycle. Comparing the gene expression profiles and DNA methylation analysis between the KYSE180 and KYSE180_HOTAIR cells revealed that only a small proportion of the methylation changes were correlated with gene expression changes. CONCLUSION:HOX transcript antisense RNA is upregulated in ESCC cell lines and patient samples, and promotes ESCC cell proliferation and tumour metastasis in mice. The knockdown of HOTAIR resulted in significant changes in gene expression, and data analysis suggested that HOTAIR-mediated gene regulation has a critical role in ESCC progression and is a novel epigenetic molecular target for treating ESCC patients.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Li X,Wu Z,Mei Q,Li X,Guo M,Fu X,Han Wdoi
10.1038/bjc.2013.548subject
Has Abstractpub_date
2013-10-15 00:00:00pages
2266-78issue
8eissn
0007-0920issn
1532-1827pii
bjc2013548journal_volume
109pub_type
杂志文章abstract::We cytogenetically investigated six osteoid osteomas, one osteoblastoma and one aggressive osteoblastoma, and observed clonal structural changes in one osteoid osteoma and in the aggressive osteoblastoma. Clonal chromosome changes had not been reported previously in osteoid osteoma, whereas the only reported chromosom...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.496
更新日期:1998-08-01 00:00:00
abstract::The association between breast and endometrial cancer was investigated in a cohort consisting of 60,065 subjects (99% of all women in whom a first breast cancer was diagnosed in Sweden in 1960-63 and 1968-81). Complete follow-up until 1981 revealed a total of 260 endometrial cancers, as against an expected number of 1...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.16
更新日期:1987-01-01 00:00:00
abstract:BACKGROUND:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS:Nu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.4
更新日期:2015-02-17 00:00:00
abstract:BACKGROUND:Paired related homoeobox 1 (PRRX1) has been identified as a new epithelial-mesenchymal transition (EMT) inducer in breast cancer. However, the function of PRRX1 in colorectal cancer (CRC) has not been elucidated. METHODS:We utilised ectopic PRRX1-expressing cell lines to analyse the function of PRRX1 in CRC...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.339
更新日期:2013-07-23 00:00:00
abstract::The aim of this study was to evaluate serum midkine (S-MK) concentrations as a prognostic tumour marker in oral squamous cell carcinoma (OSCC). We measured S-MK concentrations in patients with OSCC and healthy volunteers. In addition, we performed real-time quantitative reverse transcription-PCR analysis and immunohis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604539
更新日期:2008-08-19 00:00:00
abstract::The effect of an antiserum containing antibodies against cell surface components of PyBHK cells on the action of certain anticancer agents has been studied using a colony formation inhibition assay. The effects of x-rays, chlorambucil, CCNU and possibly ICRF 159 are augmented by the antiserum whereas methotrexate and ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.234
更新日期:1975-09-01 00:00:00
abstract::Androgen receptor (AR) signalling drives neoplastic growth and therapy resistance in prostate cancer. Recent clinical data show that docetaxel combined with androgen deprivation therapy improves outcome in hormone-sensitive disease. We studied whether testosterone and AR signalling interferes with docetaxel treatment ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01105-y
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:defective DNA repair has a causal role in hereditary colorectal cancer (CRC). Defects in the base excision repair gene MUTYH are responsible for MUTYH-associated polyposis and CRC predisposition as an autosomal recessive trait. Numerous reports have suggested MUTYH mono-allelic variants to be low penetrance ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析
doi:10.1038/sj.bjc.6605966
更新日期:2010-12-07 00:00:00
abstract::The purpose of the study is to test the hypothesis that expression of cell cycle regulatory proteins p16(INK4a) and pRb is significantly associated with prognosis in ovarian carcinomas. We performed immunohistochemical analysis of p16(INK4a) and pRb expression and correlated with survival in a series of 300 patients w...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.bjc.6603531
更新日期:2007-01-29 00:00:00
abstract:BACKGROUND:This randomised controlled trial examined the impact of screening for distress followed by two different triage methods on clinically relevant outcomes over a 12-month period. METHODS:Newly diagnosed patients attending a large tertiary cancer centre were randomised to one of the two conditions: (1) screenin...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/bjc.2012.309
更新日期:2012-08-07 00:00:00
abstract::Bryostatin 1 is a novel macrocyclic lactone activator of protein kinase C (PKC) which has clinical potential as an anti-cancer agent. The mechanism of action of this agent is unknown, but protein kinase C has been implicated. In order to investigate this possibility, we have developed P388 sublines resistant to bryost...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.353
更新日期:1994-10-01 00:00:00
abstract::In recent years, large discrepancies were described in the success rate of the tyrosinase reverse transcription polymerase chain reaction (RT-PCR) for detecting melanoma cells in the peripheral blood of melanoma patients. We present a quality control study in which we analysed the reproducibility of detection of tyros...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690436
更新日期:1999-05-01 00:00:00
abstract::In a study of 157 patients with lymphoid malignancy, the phenotype of the tumour cells was correlated with the histological classification of the tumour using the Rappaport and the Kiel classifications. The markers used included E, Fc gamma, Fc micron (IgM) and C3d rosetting, estimation of SIg and CyIg, and tests for ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.137
更新日期:1979-07-01 00:00:00
abstract:BACKGROUND:The precise timing of the angiogenic switch and the role of angiogenesis in the development of breast malignancy is currently unknown. METHODS:Therefore, the expression of CD31 (pan endothelial cells (ECs)), endoglin (actively proliferating ECs), hypoxia-inducible factor-1 (HIF-1alpha), vascular endothelial...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605196
更新日期:2009-08-18 00:00:00
abstract::Killing of autologous melanoma (auto-Me) was obtained with pooled allostimulated peripheral blood lymphocytes (PBL) in 34/42 cases and found not to be due to a cross-reactivity between melanoma and allogeneic normal antigens. To see whether generation of tumour cytotoxic PBL by allostimulation was due to release of IL...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1985.151
更新日期:1985-07-01 00:00:00
abstract::The nature of the invasive growth pattern and microvessel density (MVD) have been suggested to be predictors of prognosis in primary colorectal cancer (CRC) and colorectal liver metastases. The purpose of the present study was to determine whether these two histological features were interrelated and to assess their r...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603677
更新日期:2007-04-10 00:00:00
abstract::In this review, we discuss the recent identification in vivo of a population of CD11c+ cells exhibiting simultaneous expression of both endothelial and dendritic cell markers, termed vascular leukocytes (VLCs). VLCs are highly represented in human ovarian carcinomas and, depending on the milieu, can assemble into func...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6602476
更新日期:2005-04-11 00:00:00
abstract:BACKGROUND:Tumour carbonic anhydrase IX (CAIX), a hypoxia-inducible tumour-associated cell surface enzyme, is thought to acidify the tumour microenvironment by hydrating CO2 to form protons and bicarbonate, but there is no definitive evidence for this in solid tumours in vivo. METHODS:We used 1H magnetic resonance spe...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0216-5
更新日期:2018-08-01 00:00:00
abstract:BACKGROUND:There are phase 3 clinical trials underway evaluating anti-PD-L1 antibodies as adjuvant (postoperative) monotherapies for resectable renal cell carcinoma (RCC) and triple-negative breast cancer (TNBC); in combination with antiangiogenic VEGF/VEGFR2 inhibitors (e.g., bevacizumab and sunitinib) for metastatic ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0297-1
更新日期:2019-01-01 00:00:00
abstract::Epithelial cadherin (E-CD) is a member of the cadherin family of cell adhesion molecules and has been implicated as an invasion suppressor molecule in vitro and in vivo. We analysed 174 breast tumours from the Nottingham/Tenovus Breast Cancer Series immunohistochemically for E-CD expression using the mouse monoclonal ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2178
更新日期:2001-12-14 00:00:00
abstract:BACKGROUND:Cellular Dissociation Grade (CDG) composed of tumour budding and cell nest size has been shown to independently predict prognosis in pre-therapeutic biopsies and primary resections of oesophageal squamous cell carcinoma (ESCC). Here, we aimed to evaluate the prognostic impact of CDG in ESCC after neoadjuvant...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0623-2
更新日期:2019-12-01 00:00:00
abstract::The GER human pancreatic carcinoma cell line possesses receptors for 1,25-dihydroxyvitamin D3. We report that the vitamin D analogue EB 1089 inhibits the growth of these cells in vitro and when grown as tumour xenografts in immunodeficient mice. Tumour-bearing mice were given EB 1089 at a dose of 5 microg kg(-1) body ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.501
更新日期:1997-01-01 00:00:00
abstract::We assessed incidence and mortality of colorectal cancer (CRC) at various ages among women and men in 38 European countries. The ages at which defined levels of incidence and mortality were reached varied between 9 and 17 years between countries. This variation requires consideration in the definition of screening gui...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604488
更新日期:2008-08-05 00:00:00
abstract::Comorbid diseases can affect breast cancer prognosis. We conducted a population-based study of Danish women diagnosed with a first primary breast cancer from 1995 to 2005 (n=9300), using hospital discharge registry data to quantify comorbidities by Charlson score. We examined the influence of comorbidities on survival...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/sj.bjc.6603717
更新日期:2007-05-07 00:00:00
abstract::Sodium polyanethol sulphonate (SPS) when incorporated into rat erythrocyte lysate (REL) containing semi-solid agar medium at 1 mg ml-1. markedly enhanced colony formation by a number of anchorage-independent cell lines. REL usually needed to be included for the expression of SPS induced potentiation as in its absence ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.230
更新日期:1984-11-01 00:00:00
abstract::In 1985 a second randomisation was initiated for women in the treatment arm of the Scottish Tamoxifen Trial either to stop tamoxifen at 5 years or to continue indefinitely. A preliminary analysis of outcome in 342 patients at a median follow-up of 6 years suggests that a worthwhile gain in disease control from continu...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/bjc.1996.356
更新日期:1996-07-01 00:00:00
abstract::The pp125 focal adhesion kinase (FAK) is involved in integrin-mediated cell signalling and overexpressed in a variety of solid tumours. Focal adhesion kinase expression has been correlated to invasion and metastasis, but the data on breast cancer are inconclusive. We analysed FAK mRNA, protein levels and expression pa...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602744
更新日期:2005-09-19 00:00:00
abstract::Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603494
更新日期:2007-02-12 00:00:00
abstract::Until recently, endocrine therapy for breast cancer was relatively simple. If the tumour expressed hormone receptors, regardless of stage and age, tamoxifen was indicated. While this largely remains the case for premenopausal women, clinical trials in postmenopausal women have broadened our choice to include one of th...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6601508
更新日期:2004-01-12 00:00:00
abstract::The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n = 7) and nonmalignant (n = 7) cryoconserved breast tissue samp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603261
更新日期:2006-08-07 00:00:00