Abstract:
:MicroRNAs (miRs) are short non-coding single stranded RNAs regulating the translation of target mRNAs in normal and cancer cells in which they are frequently dysregulated promoting tumor progression. Cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC), identified by aldehyde-dehydrogenase expression (ALDH), are a cell subset within the tumor cell population that takes part in the genesis and progression of cancer. The relevance of epithelial-mesenchymal transition (EMT) has recently been recognized for tumor development and metastasis. Several studies have illustrated that miRs regulate EMT of CSC. CSC from 8 HNSCC lines, 4 of which are human papillomavirus (HPV)‑positive, were enriched by spheroid culture (spheroid-derived cells, SDC) and compared to their parental monolayer-derived cells (MDC) to analyze expression patterns of miR‑34a, CSC-related transcription factors (CSC-TFs: Sox2, Nanog, Oct3/4) and EMT-related TFs (EMT-TFs: Twist, Snail1, Snail2) by RT-qPCR. Flow cytometry was used to quantify and enrich ALDH+ CSCs. Transfection of miR‑34a mimics was used to evaluate its regulatory potential for CSC marker profiles as well as CSC- and EMT-TFs expression in HNSCC-SDC. Invasive, colony-forming and clonogenic capability of the miR‑34a mimics transfected SDC after sorting for ALDH+ and ALDH- cells was assessed by Matrigel invasion, clonogenicity and spheroid formation assay, respectively. miR‑34a expression levels were significantly downregulated in the majority of SDC derived from HNSCC-lines as compared to parental MDC (-1.6-16.4-fold). For EMT- and CSC-related TF expression, all HNSCC-derived SDC showed a significantly increased level compared to parental MDC (≤36.8-fold). Significantly increased expression of ALDH was found in SDC (2-3-fold). Compared to the HPV+, the HPV- group showed a significantly higher mean expression level of EMT-TFs, CSCs-TFs and ALDH (30.3 v.s. 12.8%). Transfection of miR‑34a mimics significantly reduced the EMT- and CSC-related TF expression level in UM-SCC9 (HPV-) and UM-SCC47 (HPV+) SDC. Simultaneously, the ALDH expression was reduced significantly (1.5-2-fold) and the invasive capacity (≤30%) and clonogenicity of HNSCC-SDC was also inhibited by transfection of miR‑34a mimics compared to controls. Restoration of miR‑34a significantly inhibited the capability for EMT formation of CSC-phenotype and functionally reduced clonogenic and invasive capacity in HNSCC cell lines. Therapeutic modulation of miR‑34a in HNSCC and CSCs may reduce the rate of metastasis and recurrence of tumors after therapy.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Sun Z,Hu W,Xu J,Kaufmann AM,Albers AEdoi
10.3892/ijo.2015.3142subject
Has Abstractpub_date
2015-10-01 00:00:00pages
1339-50issue
4eissn
1019-6439issn
1791-2423journal_volume
47pub_type
杂志文章abstract::Autoimmune diseases are the consequence of the immune system attack on the self. Autoimmunity, sometimes, is reflected through the production of autoantibodies to various self antigens leading to cellular malfunction or destruction. In the current study we employ such autoantibodies for the treatment of cancer origina...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.10.5.901
更新日期:1997-05-01 00:00:00
abstract::Double-stranded RNA-dependent protein kinase (PKR) is one of the players in the cellular antiviral responses and is involved in transcriptional stimulation through activation of NF-κB. Treatment of the human osteosarcoma cell line MG63 with the protein phosphatase inhibitor okadaic acid stimulated the expression and p...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.1911
更新日期:2013-06-01 00:00:00
abstract::Claudin 6 (CLDN6), a member of tight junction protein claudin (CLDN) family, inhibits proliferation and induces apoptosis of MCF-7 breast cancer cells. However, these molecular mechanisms of CLDN6-induced apoptosis remain largely elusive. We previously found that restoration of human CLDN6 gene expression was correlat...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3469
更新日期:2016-06-01 00:00:00
abstract::Evidence from the literature widely supports the efficacy of screening for colorectal cancer (CRC) in reducing mortality. A blood-based assay, potentially, represents a more accessible early detection tool for the identification of circulating tumour cells originating from a primary tumour site in the body. The presen...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo_00000701
更新日期:2010-08-01 00:00:00
abstract::IGF-2 mRNA binding protein 3 (IGF2BP3, IMP-3) is a well-known post-transcriptional regulatory factor of gene expression, mainly involved in embryonic development and oncogenesis. We have previously demonstrated that a subset of IMP-3 targets, such as the mRNAs of cyclins D1, D3 and G1, are positively regulated by IMP-...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3750
更新日期:2016-12-01 00:00:00
abstract::The assembly of trans-acting proteins on sequence-specific DNA cis-elements is crucial in the regulation of eukaryotic gene expression. Far upstream element binding proteins (FAB) are proteins that regulate the expression of the c-myc oncogene by binding to the far upstream element of the c-myc gene. The present study...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-09-01 00:00:00
abstract::While the effects of single growth factors on endothelial cells (ECs) have been extensively studied, the importance of induction of growth factors such as PDGF-BB (platelet derived growth factor) in ECs and its impact on tumor cell functions are only partly understood. Human umbilical vein endothelial cells (HUVECs) w...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-09-01 00:00:00
abstract::The lack of good molecular markers for diagnosis as well as treatment assessment has rendered the hepatocellular carcinoma (HCC) a major challenge in health care. In this study, woodchucks were used as an animal model for hepatitis virus-induced HCC, and gene expression studies were performed using a human oligonucleo...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Mucosa-associated lymphoid tissue (MALT) lymphomas usually involve extranodal sites, especially the stomach, lung and salivary glands. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14) (p22;q32) in MALT lymphomas, and considered to be an apoptosis-associated gene, and involves a caspase recrui...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2001-08-01 00:00:00
abstract::It has been demonstrated that triptolide inhibits the growth of several types of cancer cells in vitro and prevents tumor growth in vivo by inducing apoptosis and autophagy. Here we showed that Tripchlorolide (T4) significantly suppressed the proliferation of A549 cells in a dose- a...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1278
更新日期:2012-04-01 00:00:00
abstract::Gene therapy is a newly hatched field of biomedical research aimed at introducing therapeutically important genes into somatic cells of patients for the treatment of human disease. Whereas for inborn errors of metabolism transfer of a single gene can correct the disorder, cancer is a complex disease involving mutation...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.9.5.941
更新日期:1996-11-01 00:00:00
abstract::Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia (APL) through induction of apoptosis. To investigate the potential therapeutic usage of As2O3 in cervical cancer and its possible mechanisms, human cervical cancer cell line HeLa was employed. The cells underwent apopt...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-07-01 00:00:00
abstract::Telomerase activity was studied in 51 penile carcinomas, and detected in all samples from 3 patients with verrucous carcinoma, in 85.4% (41/48) of invasive carcinomas, in 81.8% (9/11) of adjacent non-cancerous skin and in 80% (8/10) of adjacent non-cancerous corpus cavernosum. All skin and corpus cavernosum samples fr...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.18.1.67
更新日期:2001-01-01 00:00:00
abstract::Optimal conditions have been defined to grow primary cultures of malignant melanoma suitable for in vitro pharmacological studies. A feasibility of primary cultures was observed in 60% of 62 clinical melanoma lymph node metastases. The neoplastic nature of the cells grown in culture, as assessed by the highly specific...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.1.6.619
更新日期:1992-11-01 00:00:00
abstract::The protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved and activated by trypsin and tryptase. The purpose of this study was to clarify the role of PAR-2 in proliferation of human pancreatic cancer cells. PAR-2 mRNA and protein expression were detected by RT-PCR and Western blotting i...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-06-01 00:00:00
abstract::Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency rel...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-06-01 00:00:00
abstract::Reports of the metabolomic characteristics of esophageal cancer are limited. In the present study, we thus conducted metabolome analysis of paired tumor tissues (Ts) and non-tumor esophageal tissues (NTs) using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). The Ts and surrounding NTs were surgi...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2018.4340
更新日期:2018-06-01 00:00:00
abstract::Gliomas are malignant brain tumors thought to arise through multi-step tumorigenesis, involving both the activation of oncogenes and the loss of tumor suppressor genes. The cyclin D1 gene encodes a proto-oncogenic cell cycle regulator implicated in the pathogenesis of several types of cancer, including gliomas. Northe...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.9.3.493
更新日期:1996-09-01 00:00:00
abstract::3F8 is an IgG3 murine monoclonal antibody directed against the ganglioside GD2. In a phase II study, 3F8 was administered i.v. to 16 patients (pts) who had stage 4 neuroblastoma. Response was seen in bony lesions (2 of 7 pts) and marrow (3 of 8 pts). Acute toxicities of pain, fever, urticaria, hypertension, hypotensio...
journal_title:International journal of oncology
pub_type: 临床试验,杂志文章
doi:10.3892/ijo.12.6.1299
更新日期:1998-06-01 00:00:00
abstract::The molecular basis of host-tumor interaction in HLA-A31+ cancer patients has not been well understood. This lack of clarification is hampering the development of specific immunotherapies for these patients. This study aimed to identify a set of CTL-epitope peptides applicable for the specific immunotherapy of cancer ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-02-01 00:00:00
abstract::Prostate cancer, the third most common cancer in men worldwide, varies substantially according to geographic region and race/ethnicity. Obesity and associated endocrine variation are foremost among the risk factors that may underlie these regional and ethnic differences. The association between obesity and prostate ca...
journal_title:International journal of oncology
pub_type: 杂志文章,评审
doi:
更新日期:2006-03-01 00:00:00
abstract::Early-onset breast cancer is one of the most common malignancies and causes of death among young women, and its incidence is increasing. In the present study, we aimed to investigate the epigenetic modifications of the breast cancer type 1 susceptibility gene (BRCA1) in breast tissues and blood cells derived from wome...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1021
更新日期:2011-07-01 00:00:00
abstract::Tetramethypyrazine (TMP), one of the active compounds extracted from the traditional Chinese medicinal herb (Chuanxiong), has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms have not been fully elucidated. In the present study, the anticancer ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3670
更新日期:2016-10-01 00:00:00
abstract::Cancer cells genetically modified to secrete immunoregulatory cytokines offer great promise for human cancer treatment as tumor vaccines. However, in preclinical animal studies, large established cancer burdens have appeared difficult to eradicate with such vaccines. For example, lethally-irradiated GM-CSF-secreting C...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.1.161
更新日期:1998-01-01 00:00:00
abstract::We investigated the relationship between cell growth and differentiation and COX-2 expression in oral squamous cell carcinoma (SCC) in vitro and in vivo. Treatment of SCC25 oral squamous carcinoma cells with sodium butyrate (SB) at 0.5-5 mM or all-trans retinoic acid (ATRA) at 3-300 microM inhibited cell growth and in...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2005-02-01 00:00:00
abstract::Following the publication of this article, the authors noted that there was an error in Fig. 4. The lines representing the two groups were indicated incorrectly in all graphs in Fig. 4. A corrected version of Fig. 4 is presented below. Furthermore, we regret any inconvenience this error may have caused. [the original ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3796
更新日期:2017-02-01 00:00:00
abstract::Dihydropyrimidine dehydrogenase (DPD) is the first and rate-limiting enzyme in the degradation of pyrimidines and pyrimidine base analogs including the anticancer drugs 5-fluorouracil (5-FU) and Xeloda. A decreased DPD enzyme activity has been described in cancer patients experiencing severe and life-threatening toxic...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2003-02-01 00:00:00
abstract::Sirtuin 6 (SIRT6) is a member of the sirtuin deacetylases (sirtuins), which are derivatives of the yeast Silent information regulator 2 (Sir2) protein. SIR2 and its mammalian derivatives play a central role in epigenetic gene silencing, recombination, metabolism, cell differentiation and in the regulation of aging. In...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-02-01 00:00:00
abstract::Changes in the expression of the putative p53-inducible inhibitor p21 of cyclin-dependent kinase (CDK) and p21-associated CDK activity were examined in relation to the DNA synthesis-associated nuclear exclusion of p53 after stimulating growth arrested human breast cancer MCF7 cells with serum. Following stimulation, p...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.5.1059
更新日期:1994-11-01 00:00:00
abstract::The proteins of the rho gene family have been isolated from cytosolic as well as particulate fractions. The rho proteins have values of about 22KDa and have consensus amino acid sequences for GTP/GDP-binding and GTPase activities. We have localized the rho proteins in mammalian cells by using affinity-purified anti-pe...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.3.6.1103
更新日期:1993-12-01 00:00:00