MicroRNA response to hypoxic stress in soft tissue sarcoma cells: microRNA mediated regulation of HIF3α.

Abstract:

BACKGROUND:Hypoxia is often encountered in solid tumors and known to contribute to aggressive tumor behavior, radiation- and chemotherapy resistance resulting in a poor prognosis for the cancer patient. MicroRNAs (miRNAs) play a role in the regulation of the tumor cell response to hypoxia, however, not much is known about the involvement of miRNAs in hypoxic signalling pathways in soft tissue sarcomas (STS). METHOD:A panel of twelve STS cell lines was exposed to atmospheric oxygen concentrations (normoxia) or 1% oxygen (hypoxia) for up to 48 h. Hypoxic conditions were verified and miRNA expression profiles were assessed by LNA™ oligonucleotide microarrays and RT-PCR after 24 h. The expression of target genes regulated by hypoxia responsive miRNAs is examined by end-point PCR and validated by luciferase reporter constructs. RESULTS:Exposure of STS cell lines to hypoxic conditions gave rise to upregulation of Hypoxia Inducible Factor (HIF) 1α protein levels and increased mRNA expression of HIF1 target genes CA9 and VEGFA. Deregulation of miRNA expression after 24 h of hypoxia was observed. The most differentially expressed miRNAs (p<0.001) in response to hypoxia were miR-185-3p, miR-485-5p, miR-216a-5p (upregulated) and miR-625-5p (downregulated). The well-known hypoxia responsive miR-210-3p could not be reliably detected by the microarray platform most likely for technical reasons, however, its upregulation upon hypoxic stress was apparent by qPCR. Target prediction algorithms identified 11 potential binding sites for miR-485-5p and a single putative miR-210-3p binding site in the 3'UTR of HIF3α, the least studied member of the HIF family. We showed that HIF3α transcripts, expressing a 3'UTR containing the miR-485-5p and miR-210-3p target sites, are expressed in all sarcoma cell lines and upregulated upon hypoxia. Additionally, luciferase reporter constructs containing the 3'UTR of HIF3α were used to demonstrate regulation of HIF3α by miR-210-3p and miR-485-5p. CONCLUSION:Here we provide evidence for the miRNA mediated regulation of HIF3α by hypoxia responsive miRNAs in STS, which may help to tightly regulate and fine-tune the hypoxic response. This provides a better insight into the mechanisms underlying the hypoxic response in STS and may ultimately yield information on novel prognostic and predictive markers or targets for treatment.

journal_name

BMC Cancer

journal_title

BMC cancer

authors

Gits CM,van Kuijk PF,de Rijck JC,Muskens N,Jonkers MB,van IJcken WF,Mathijssen RH,Verweij J,Sleijfer S,Wiemer EA

doi

10.1186/1471-2407-14-429

subject

Has Abstract

pub_date

2014-06-13 00:00:00

pages

429

issn

1471-2407

pii

1471-2407-14-429

journal_volume

14

pub_type

杂志文章
  • The study protocol of the evaluation for the preventive efficacy of the HPV vaccine for persistent HPV16/18 infection in Japanese adult women: the HAKUOH study.

    abstract:BACKGROUND:In general, human papillomavirus (HPV) vaccines have demonstrated efficacy in young women worldwide, but there is limited evidence on the efficacy of the quadrivalent HPV6/11/16/18 vaccine in adult women and no evidence of its effectiveness in Japanese adult women in particular. This study aims to evaluate t...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-020-07563-0

    authors: Kurokawa T,Yamamoto M,Onuma T,Tsuyoshi H,Shinagawa A,Chino Y,Yoshida Y

    更新日期:2020-11-03 00:00:00

  • TGF-beta receptor 2 downregulation in tumour-associated stroma worsens prognosis and high-grade tumours show more tumour-associated macrophages and lower TGF-beta1 expression in colon carcinoma: a retrospective study.

    abstract:BACKGROUND:Histological phenotype and clinical behaviour of malignant tumours are not only dependent on alterations in the epithelial cell compartment, but are affected by their interaction with inflammatory cells and tumour-associated stroma. Studies in animal models have shown influence of tumour-associated macrophag...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-7-156

    authors: Bacman D,Merkel S,Croner R,Papadopoulos T,Brueckl W,Dimmler A

    更新日期:2007-08-10 00:00:00

  • Synergistic inhibition of tumor growth by combination treatment with drugs against different subpopulations of glioblastoma cells.

    abstract:BACKGROUND:Glioma stem cells (GSCs) contribute to tumor recurrence and drug resistance. This study characterizes the tumorigenesis of CD133+ cells and their sensitivity to pharmacological inhibition. METHODS:GSCs from human U87 and rat C6 glioblastoma cell lines were isolated via magnetic cell sorting using CD133 as a...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-017-3924-y

    authors: Chang CH,Liu WT,Hung HC,Gean CY,Tsai HM,Su CL,Gean PW

    更新日期:2017-12-29 00:00:00

  • Identification of S100A8-correlated genes for prediction of disease progression in non-muscle invasive bladder cancer.

    abstract:BACKGROUND:S100 calcium binding protein A8 (S100A8) has been implicated as a prognostic indicator in several types of cancer. However, previous studies are limited in their ability to predict the clinical behavior of the cancer. Here, we sought to identify a molecular signature based on S100A8 expression and to assess ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-10-21

    authors: Kim SK,Kim EJ,Leem SH,Ha YS,Kim YJ,Kim WJ

    更新日期:2010-01-25 00:00:00

  • The pemetrexed-containing treatments in the non-small cell lung cancer is -/low thymidylate synthase expression better than +/high thymidylate synthase expression: a meta-analysis.

    abstract:BACKGROUND:The predictive value of thymidylate synthase (TS) for clinical sensitivity to pemetrexed-containing chemotherapy in patients with non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis is performed to provide an assessment of whether expression variations of TS are associated with objec...

    journal_title:BMC cancer

    pub_type: 杂志文章,meta分析,评审

    doi:10.1186/1471-2407-14-205

    authors: Wang L,Wang R,Pan Y,Sun Y,Zhang J,Chen H

    更新日期:2014-03-19 00:00:00

  • A machine learning approach to optimizing cell-free DNA sequencing panels: with an application to prostate cancer.

    abstract:BACKGROUND:Cell-free DNA's (cfDNA) use as a biomarker in cancer is challenging due to genetic heterogeneity of malignancies and rarity of tumor-derived molecules. Here we describe and demonstrate a novel machine-learning guided panel design strategy for improving the detection of tumor variants in cfDNA. Using this app...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-020-07318-x

    authors: Cario CL,Chen E,Leong L,Emami NC,Lopez K,Tenggara I,Simko JP,Friedlander TW,Li PS,Paris PL,Carroll PR,Witte JS

    更新日期:2020-08-28 00:00:00

  • Education level as a predictor of survival in patients with multiple myeloma.

    abstract:BACKGROUND:Disparities in multiple myeloma (MM) prognosis based on sociodemographic factors may exist. We investigated whether education level at diagnosis influenced Chinese MM patient outcomes. METHODS:We performed a multicenter retrospective analysis of data from 773 MM patients across 9 centers in China from 2006 ...

    journal_title:BMC cancer

    pub_type: 杂志文章,多中心研究

    doi:10.1186/s12885-020-07178-5

    authors: Xu L,Wang X,Pan X,Wang X,Wang Q,Wu B,Cai J,Zhao Y,Chen L,Li W,Li J

    更新日期:2020-08-08 00:00:00

  • KIAA0101 (OEACT-1), an expressionally down-regulated and growth-inhibitory gene in human hepatocellular carcinoma.

    abstract:BACKGROUND:Our previous cDNA array results indicated KIAA0101 as one of the differentially expressed genes in human hepatocellular carcinoma (HCC) as compared with non-cancerous liver. However, it is necessary to study its expression at protein level in HCC and its biological function for HCC cell growth. METHOD:Weste...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-6-109

    authors: Guo M,Li J,Wan D,Gu J

    更新日期:2006-04-29 00:00:00

  • The role of brevican in glioma: promoting tumor cell motility in vitro and in vivo.

    abstract:BACKGROUND:Malignant glioma is a common primary tumor of the central nervous system. Brevican, an abundant extracellular matrix component in the adult brain, plays a critical role in the process of glioma. The mechanisms for the highly invasive behavior of gliomas are still poorly understood. The aim of this study was ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-12-607

    authors: Lu R,Wu C,Guo L,Liu Y,Mo W,Wang H,Ding J,Wong ET,Yu M

    更新日期:2012-12-19 00:00:00

  • EGFR exon 20 insertion mutations and response to osimertinib in non-small-cell lung cancer.

    abstract:BACKGROUND:Epidermal growth factor receptor exon 20 insertion (EGFRex20ins) mutations represent approximately 4-12% of EGFR mutations and are generally refractory to the 1st and 2nd generation EGFR tyrosine kinase inhibitors (TKIs). Development of effective therapies for patients with EGFRex20ins mutant non-small-cell ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-019-5820-0

    authors: Fang W,Huang Y,Hong S,Zhang Z,Wang M,Gan J,Wang W,Guo H,Wang K,Zhang L

    更新日期:2019-06-17 00:00:00

  • Comprehensive gene expression analysis for exploring the association between glucose metabolism and differentiation of thyroid cancer.

    abstract:BACKGROUND:The principle of loss of iodine uptake and increased glucose metabolism according to dedifferentiation of thyroid cancer is clinically assessed by imaging. Though these biological properties are widely applied to appropriate iodine therapy, the understanding of the genomic background of this principle is sti...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-019-6482-7

    authors: Suh HY,Choi H,Paeng JC,Cheon GJ,Chung JK,Kang KW

    更新日期:2019-12-30 00:00:00

  • Investigating the performance and cost-effectiveness of the simple ultrasound-based rules compared to the risk of malignancy index in the diagnosis of ovarian cancer (SUBSONiC-study): protocol of a prospective multicenter cohort study in the Netherlands.

    abstract:BACKGROUND:Estimating the risk of malignancy is essential in the management of adnexal masses. An accurate differential diagnosis between benign and malignant masses will reduce morbidity and costs due to unnecessary operations, and will improve referral to a gynecologic oncologist for specialized cancer care, which im...

    journal_title:BMC cancer

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1186/s12885-015-1319-5

    authors: Meys EM,Rutten IJ,Kruitwagen RF,Slangen BF,Bergmans MG,Mertens HJ,Nolting E,Boskamp D,Beets-Tan RG,van Gorp T

    更新日期:2015-06-26 00:00:00

  • Correction to: Human papillomavirus type 18 oncoproteins exert their oncogenicity in esophageal and tongue squamous cell carcinoma cell lines distinctly.

    abstract::Following publication of the original article [1], the authors reported that during the production process, Table 1 was omitted. ...

    journal_title:BMC cancer

    pub_type: 杂志文章,已发布勘误

    doi:10.1186/s12885-019-6493-4

    authors: Boon SS,Chen Z,Li J,Lee KYC,Cai L,Zhong R,Chan PKS

    更新日期:2019-12-29 00:00:00

  • Sensitive HPV detection in oropharyngeal cancers.

    abstract:BACKGROUND:Human papillomaviruses (HPV) are the aetiological agents of certain benign and malignant tumours of skin and mucosae; the most important of which is cervical cancer. Also, the incidence of ano-genital warts, HPV-anal cancer and oropharyngeal cancers are rising. To help ascertain a useful PCR detection protoc...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-9-440

    authors: Winder DM,Ball SL,Vaughan K,Hanna N,Woo YL,Fränzer JT,Sterling JC,Stanley MA,Sudhoff H,Goon PK

    更新日期:2009-12-15 00:00:00

  • Cancer incidence and mortality in Serbia 1999-2009.

    abstract:BACKGROUND:Despite the increase in cancer incidence in the last years in Serbia, no nation-wide, population-based cancer epidemiology data have been reported. In this study cancer incidence and mortality rates for Serbia are presented using nation-wide data from two population-based cancer registries. These rates are a...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-13-18

    authors: Mihajlović J,Pechlivanoglou P,Miladinov-Mikov M,Zivković S,Postma MJ

    更新日期:2013-01-15 00:00:00

  • Efficacy and safety profile of nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic cancer treated to disease progression: a subanalysis from a phase 3 trial (MPACT).

    abstract:BACKGROUND:The phase 3 MPACT trial in patients with metastatic pancreatic cancer demonstrated superior efficacy of nab-paclitaxel (nab-P) + gemcitabine (Gem) vs Gem monotherapy for all endpoints examined including overall survival, the primary endpoint. In the MPACT trial, patients were treated until progressive diseas...

    journal_title:BMC cancer

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/s12885-016-2798-8

    authors: Vogel A,Römmler-Zehrer J,Li JS,McGovern D,Romano A,Stahl M

    更新日期:2016-10-21 00:00:00

  • Comparison of analytical and clinical performance of CLART HPV2 genotyping assay to Linear Array and Hybrid Capture 2: a split-sample study.

    abstract:BACKGROUND:Human Papillomavirus (HPV) genotyping has an increasingly important role in cervical cancer screening and vaccination monitoring, however, without an internationally agreed standard reference assay. The test results from the most widely used genotyping assays are read manually and hence prone to inter-observ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-015-1223-z

    authors: Ejegod DM,Rebolj M,Bonde J

    更新日期:2015-04-02 00:00:00

  • The effects of shared decision-making compared to usual care for prostate cancer screening decisions: a systematic review and meta-analysis.

    abstract:BACKGROUND:Shared decision-making (SDM) is recommended for men facing prostate cancer (PC) screening decisions. We synthesize the evidence on the comparative effectiveness of SDM with usual care. METHODS:We searched academic and grey literature databases, and other sources for primary randomised controlled trials (RCT...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-018-4794-7

    authors: Martínez-González NA,Neuner-Jehle S,Plate A,Rosemann T,Senn O

    更新日期:2018-10-22 00:00:00

  • Prognostic significance of classified extramural tumor deposits and extracapsular lymph node invasion in T3-4 colorectal cancer: a retrospective single-center study.

    abstract:BACKGROUND:Extramural tumor deposits (TDs) and extracapsular lymph node involvement (ECLNI) are considered to be poor prognostic factors in patients with T3-4, N0-2, M0 colorectal cancer (CRC). Although TDs are known to have multiple origins and pleomorphic features, the prognostic significances of the different type o...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-015-1885-6

    authors: Yamano T,Semba S,Noda M,Yoshimura M,Kobayashi M,Hamanaka M,Beppu N,Yano A,Tsukamoto K,Matsubara N,Tomita N

    更新日期:2015-11-06 00:00:00

  • The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription.

    abstract:BACKGROUND:Inducible nitric oxide synthase (iNOS) metabolizes L-arginine to produce nitric oxide (NO) which was originally identified in myeloid cells as a host defense mechanism against pathogens. Recent studies, however, have revealed that iNOS is often induced in tumor cells and myeloid cells in the tumor microenvir...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-015-1808-6

    authors: Simon PS,Sharman SK,Lu C,Yang D,Paschall AV,Tulachan SS,Liu K

    更新日期:2015-10-23 00:00:00

  • Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy.

    abstract:BACKGROUND:Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. METHODS:A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surge...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-019-6261-5

    authors: Trotsyuk I,Sparschuh H,Müller AJ,Neumann K,Kruschewski M,Horst D,Elezkurtaj S

    更新日期:2019-11-01 00:00:00

  • Prostate cancer-specific survival among warfarin users in the Finnish Randomized Study of Screening for Prostate Cancer.

    abstract:BACKGROUND:Venous thromboembolic events (VTE) are common in cancer patients and associated with higher mortality. In vivo thrombosis and anticoagulation might be involved in tumor growth and progression. We studied the association of warfarin and other anticoagulant use as antithrombotic medication and prostate cancer ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-017-3579-8

    authors: Kinnunen PTT,Murtola TJ,Talala K,Taari K,Tammela TLJ,Auvinen A

    更新日期:2017-08-29 00:00:00

  • Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment.

    abstract:BACKGROUND:Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor tr...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-3-21

    authors: Bathe OF,Dalyot-Herman N,Malek TR

    更新日期:2003-07-28 00:00:00

  • A novel circular invasion assay mimics in vivo invasive behavior of cancer cell lines and distinguishes single-cell motility in vitro.

    abstract:BACKGROUND:Classical in vitro wound-healing assays and other techniques designed to study cell migration and invasion have been used for many years to elucidate the various mechanisms associated with metastasis. However, many of these methods are limited in their ability to achieve reproducible, quantitative results th...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/1471-2407-8-198

    authors: Kam Y,Guess C,Estrada L,Weidow B,Quaranta V

    更新日期:2008-07-14 00:00:00

  • Women's knowledge of and attitudes toward cervical cancer and cervical cancer screening in Zanzibar, Tanzania: a cross-sectional study.

    abstract:BACKGROUND:Cervical cancer is the most common cancer and the leading cause of cancer death among women in Tanzania. Knowledge of and willingness to receive a cervical cancer screening are important determinants of prevention. This study aimed to describe women's awareness of cervical cancer and to explore the attitudes...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-020-6528-x

    authors: Weng Q,Jiang J,Haji FM,Nondo LH,Zhou H

    更新日期:2020-01-28 00:00:00

  • Adaptive radiotherapy in locally advanced esophageal cancer with atelectasis: a case report.

    abstract:BACKGROUND:To the best of our knowledge, no study has reported mediastinal shift accompanied with obstructive atelectasis due to bulky primary esophageal tumor components treated with adaptive radiotherapy and concurrent chemotherapy. CASE PRESENTATION:Here we report the case of a 65-year-old male patient diagnosed wi...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-019-6505-4

    authors: Sakanaka K,Fujii K,Mizowaki T

    更新日期:2020-01-06 00:00:00

  • Identification of a unique hepatocellular carcinoma line, Li-7, with CD13(+) cancer stem cells hierarchy and population change upon its differentiation during culture and effects of sorafenib.

    abstract:BACKGROUNDS:Cancer stem cell (CSC) research has highlighted the necessity of developing drugs targeting CSCs. We investigated a hepatocellular carcinoma (HCC) cell line that not only has CSC hierarchy but also shows phenotypic changes (population changes) upon differentiation of CSC during culture and can be used for s...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-015-1297-7

    authors: Yamada T,Abei M,Danjoh I,Shirota R,Yamashita T,Hyodo I,Nakamura Y

    更新日期:2015-04-11 00:00:00

  • ZFP36 stabilizes RIP1 via degradation of XIAP and cIAP2 thereby promoting ripoptosome assembly.

    abstract:BACKGROUND:ZFP36 is an mRNA binding protein that exerts anti-tumor activity in glioblastoma by triggering cell death, associated to an increase in the stability of the kinase RIP1. METHODS:We used cell death assays, size exclusion chromatography, Co-Immunoprecipitation, shRNA lentivectors and glioma neural stem cells ...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-015-1388-5

    authors: Selmi T,Alecci C,dell' Aquila M,Montorsi L,Martello A,Guizzetti F,Volpi N,Parenti S,Ferrari S,Salomoni P,Grande A,Zanocco-Marani T

    更新日期:2015-05-06 00:00:00

  • In vitro and in silico validation of CA3 and FHL1 downregulation in oral cancer.

    abstract:BACKGROUND:Aberrant methylation is a frequent event in oral cancer. METHODS:In order to better characterize these alterations, a search for genes downregulated by aberrant methylation in oral squamous cell carcinoma (OSCC) was conducted through the mining of ORESTES dataset. Findings were further validated in OSCC cel...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-018-4077-3

    authors: Pereira CM,de Carvalho AC,da Silva FR,Melendez ME,Lessa RC,Andrade VCC,Kowalski LP,Vettore AL,Carvalho AL

    更新日期:2018-02-17 00:00:00

  • Factors predictive of invasive ductal carcinoma in cases preoperatively diagnosed as ductal carcinoma in situ.

    abstract:BACKGROUND:Invasion is often found during postoperative pathological examination of cases diagnosed as ductal carcinoma in situ (DCIS) by histological examinations such as core needle biopsy (CNB) or vacuum-assisted biopsy (VAB). A meta-analysis reported that 25.9% of invasive ductal carcinoma (IDC) cases are preoperat...

    journal_title:BMC cancer

    pub_type: 杂志文章

    doi:10.1186/s12885-020-07001-1

    authors: Takada K,Kashiwagi S,Asano Y,Goto W,Morisaki T,Takahashi K,Fujita H,Takashima T,Tomita S,Hirakawa K,Ohira M

    更新日期:2020-06-03 00:00:00