Abstract:
:Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with broad resistance to chemotherapeutic drugs. Krüppel-like factor 4 (KLF4) is a candidate tumor suppressor in PDAC. However, the precise role of KLF4 in gemcitabine resistance of PDAC remains largely unclear. In this study, we demonstrated that gemcitabine inhibited KLF4 expression. Moreover, gemcitabine also reduced the levels of miR‑200b and miR‑183, but promoted ZEB1 expression in PDAC cells. KLF4 knockdown blocked the expression of miR‑200b and miR‑183, and inversely, KLF4 overexpression promoted the expression of miR‑200b and miR‑183, suggesting that KLF4 positively regulated the expression of miR‑200b and miR‑183. Moreover, KLF4 knockdown enhanced ZEB1 expression and gemcitabine resistance while KLF4 overexpression induced the opposite effect. ChIP assays verified that KLF4 positively regulated the expression of miR‑200b and miR‑183 by directly binding to their promoters. Then, miR‑200b and miR‑183 directly inhibited ZEB1 expression by targeting its 3'UTR region. ZEB1 knockdown attenuated gemcitabine resistance in PDAC cells. KLF4 overexpression promoted gemcitabine sensitivity of PDAC in vivo by negatively regulating ZEB1 expression. Our results revealed that novel crosstalk between KLF4 and ZEB1 regulated gemcitabine resistance in PDAC.
journal_name
Int J Oncoljournal_title
International journal of oncologyauthors
Wang Z,Chen Y,Lin Y,Wang X,Cui X,Zhang Z,Xian G,Qin Cdoi
10.3892/ijo.2017.4099subject
Has Abstractpub_date
2017-10-01 00:00:00pages
1239-1248issue
4eissn
1019-6439issn
1791-2423journal_volume
51pub_type
杂志文章abstract::MicroRNA‑301a (miRNA/miR‑301a) and nuclear factor (NF)‑κB signaling play important roles in tumor invasion, migration and progression. However, the role of miRNA‑301a‑3p in human gastric cancer (GC), and specifically in the activation of NF‑κB signaling, remains unclear. The aim of the present study was to investigate...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5072
更新日期:2020-08-01 00:00:00
abstract::Many genes that are frequently mutated in human cancer are known to be involved in the control of normal cellular proliferation. One of the genes involved in DNA mismatch repair is hMLH1, defective mutations of which are found in some familial and various sporadic cancers. Although the DNA mismatch repair activity of ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.12.3.609
更新日期:1998-03-01 00:00:00
abstract::The enzyme poly(ADP-ribose)polymerase (PARP) has been implicated in several cellular processes by the demonstration of ADP-ribosylation of proteins which play a role in cellular repair of DNA damage, response to ionizing radiation and apoptosis. In addition, ADP-ribosylation has been shown to play a role in cell cycle...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.8.4.803
更新日期:1996-04-01 00:00:00
abstract::A disintegrin and metalloproteinase-17 (ADAM17) can cut and release a wide variety of epidermal growth factor receptor (EGFR) ligands to promote survival, invasion and proliferation of cancer cell, and therefore, is considered to be a potential therapeutic target for cancer. The main goal of the present study was to o...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3536
更新日期:2016-08-01 00:00:00
abstract::Pancreatic neuroendocrine neoplasms (p-NENs) are slowly growing tumors with frequent liver metastasis. There is a variety of approaches to treat non-functional p-NENs with synchronous liver metastasis (LM) which complicates the determination of optimal treatment. Based on updated literature review, we discussed the tr...
journal_title:International journal of oncology
pub_type: 共识发展会议,杂志文章
doi:10.3892/ijo.2016.3711
更新日期:2016-11-01 00:00:00
abstract::Effects of vorozole, a potent and specific non-steroidal aromatase inhibitor, were evaluated on female Sprague-Dawley (SD) rats with 7, 12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. Vorozole at a dose of 0.25, 1.0 and 4.0 mg/kg was orally administered once a day for 28 consecutive days. A significant reg...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:1999-02-01 00:00:00
abstract::Genetically engineered stem cells (GESTECs) producing suicide enzymes and immunotherapeutic cytokines have therapeutic effects on tumors, and may possibly reduce the side effects of toxic drugs used for treatments. Suicide enzymes can convert non-toxic pro-drugs to toxic metabolites that can reduce tumor growth. Cytos...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.1288
更新日期:2012-04-01 00:00:00
abstract::Cell division cycle 20 (CDC20) encodes a regulatory protein interacting with the anaphase-promoting complex/cyclosome (APC/C) in the cell cycle and plays important roles in tumorigenesis and progression of multiple tumors. The present study aimed to investigate the clinical significance of CDC20 in hepatocellular carc...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2559
更新日期:2014-10-01 00:00:00
abstract::We have demonstrated anti-proliferation and anti-metastasis effects of both interferon-alpha and a histone deacetylase inhibitor, sodium butyrate, on human liver cancer cell lines. In this study, invasive ability of human liver cancer cell lines through the matrix-coated membrane was examined and inhibitory effect of ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-04-01 00:00:00
abstract::On the basis of the gene expression profiles of 120 lung cancer cases using a cDNA microarray containing 27,648 genes or expressed sequence tags (ESTs), we identified LRRC42 (Leucine-rich repeat containing 42) to be significantly upregulated in the majority of lung cancers. Northern blot analysis demonstrated that LRR...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2418
更新日期:2014-07-01 00:00:00
abstract::PDZ-domain protein GIPC1/GIPC interacts with GTPase-activating protein RGS-GAIP, TGFbeta type III receptor, and integrin alpha6A subunit. Kermit, a Xenopus orthologue of human GIPC1, interacts with some class of WNT receptor. In this study, we identified a novel GIPC1-related gene in human genome by using bioinformati...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2002-03-01 00:00:00
abstract::The presence of arachidonate 12-lipoxygenase (12-LOX) potentiates prostate cancer (PCa) progression and therefore may be a good therapeutic target and/or a potential diagnostic predictor for PCa. In this study, we examined the expression of 12-LOX in PCa stem cells (PCa SCs) to test if it can serve as a unique marker ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.901
更新日期:2011-04-01 00:00:00
abstract::A number of glycosyltransferases have been identified and biologically characterized in cancer cells, yet their exact pathophysiological functions are largely unknown. Here, we report the critical role of β1,3-N-acetylgalactosaminyltransferase II (B3GALNT2), which transfers N-acetylgalactosamine (GalNAc) in a β1,3 lin...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2013.2187
更新日期:2014-02-01 00:00:00
abstract::Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. However, extended TAM administration for breast cancer induces increased VEGF levels in patients, promoting new blood vessel formation and thereby limiting its efficacy and highlighting ...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2014.2299
更新日期:2014-04-01 00:00:00
abstract::Activation of the Wingless (Wnt)/ß-catenin signaling pathway contributes to prostate tumorigenesis and metastasis. Depending of the stage of prostate cancer development, current drug therapies are of limited efficiency, so that prevention with natural compounds appears as an attractive strategy especially due to the s...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2011.905
更新日期:2011-03-01 00:00:00
abstract::Irvalec® (elisidepsin trifluoroacetate, PM02734) is a novel marine-derived cyclic peptide belonging to the Kahaladide family of compounds, currently in clinical trials with preliminary evidence of antitumor activity. Previous studies have shown a correlation between elisidepsin sens...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1425
更新日期:2012-07-01 00:00:00
abstract::Cytokine expression in a tumor microenvironment can impact both host defense against the tumor and tumor cell survival. In this study, we sought to clarify whether the cytokine gene expression profile could have clinical associations with ovarian cancer. We analyzed the expression of 16 cytokine genes (IL-1α, IL-1β, I...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1533
更新日期:2012-09-01 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::Previous studies have revealed that protein kinase C (PKC) is responsible for malignant progression. In the present study, we investigated the potent inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly enhanced alph...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.13.5.981
更新日期:1998-11-01 00:00:00
abstract::A promising family of anticancer agents, the camptothecins, is noted for their ability to induce apoptosis specifically in malignant cells. However, a major obstacle for successful cancer treatment by these and other chemotherapeutic agents is the intrinsic or acquired resistance to drug treatment. Resistance to 9NC6,...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-08-01 00:00:00
abstract::As epidemiological data suggest ultraviolet (UV) radiation to be the major environmental factor for the development of melanoma, we screened this malignancy for UV-specific C right curved arrow T and CC right curved arrow TT DNA mutations as described in squamous and basal cell carcinomas of the skin. Mitochondrial (m...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2004-01-01 00:00:00
abstract::Glioblastomas are highly vascularized tumors and anti-angiogenic strategy is one of the most promising therapeutic approaches to treat brain tumors. Interferon alpha (IFN-alpha) as a single agent or combined with standard chemo-therapy has been shown to inhibit various tumors, but the effect of combination anti-angiog...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2006-06-01 00:00:00
abstract::Recently, the compilation of massive amounts of genetic and genomic information on a wide variety of human cancer types, collectively known as The Cancer Genome Atlas (TCGA), has revealed a wealth of descriptive classification schemes both within and between different types and sources of cancer. In endometrial cancer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2020.5139
更新日期:2020-12-01 00:00:00
abstract::Cutaneous infantile hemangioma progresses through proliferation and involution phases. Since treatment with interferon, a negative regulator of angiogenesis, accelerates the involution phase, we hypothesized that cutaneous infantile hemangioma is associated with an imbalance between endogenous positive and negative re...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.14.3.401
更新日期:1999-03-01 00:00:00
abstract::The murine double minute-2 (MDM2) gene encodes a 90 kDa protein which binds and inactivates the protein product of the p53 tumor suppressor gene. To elucidate the potential role of MDM2 in benign and malignant hyperproliferative conditions in the pancreas, we studied MDM2 expression in cultured human pancreatic cancer...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.5.6.1279
更新日期:1994-12-01 00:00:00
abstract::Interferon (IFN) is a promising drug for prevention and treatment of hepatocellular carcinoma (HCC) in combination with chemotherapeutic agents. We previously reported that the spectra of antiproliferative activity and synergistic effect of IFN-beta when combined with anticancer drugs are more potent than those of IFN...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract::Human carcinogenesis is a multistep process in which epithelial cells progress through a series of premalignant phenotypes until an invasive cancer emerges. Extensive experimental observations in carcinogenesis have demonstrated this process can be divided into three general eras: initiation, promotion, and progressio...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:
更新日期:2008-04-01 00:00:00
abstract::We purified and identified eight xanthones from mangosteen (Garcinia mangostana L.) and investigated whether these compounds inhibited the activities of mammalian DNA polymerases (Pols) and human DNA topoisomerases (Topos). β-Mangostin was the strongest inhibitor of both mammalian Pols and human Topos among the isolat...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3321
更新日期:2016-03-01 00:00:00
abstract::Polo-like kinase 1 (PLK1), a serine/threonine kinase and an oncogene, is crucial in regulating cell cycle progression. PLK1 also has been demonstrated as a potential target of osteosarcoma (OS) by using short hairpin RNA libraries in lentiviral vectors for screening of protein kinase. In preclinical studies, GSK461364...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2016.3352
更新日期:2016-03-01 00:00:00
abstract::Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. To evaluate the efficacy of dietary resveratrol in vivo, 5-week-old NOD.CB17-Prkdcscid/J mice were fed a control diet or a d...
journal_title:International journal of oncology
pub_type: 杂志文章
doi:10.3892/ijo.2012.1650
更新日期:2012-12-01 00:00:00