Abstract:
:Protein inhibitor of activated STAT3 (PIAS3) is an endogenous suppressor of signal transducer and activator of transcription 3 (STAT3) signaling. By directly interacting with phosphorylated STAT3, PIAS3 can block the downstream transcriptional activity of STAT3, which is hyper-activated in various cancers. We previously reported that in malignant mesothelioma (MM), low PIAS3 expression is associated with increased STAT3 activation and correlates with poor patient survival, yet the regulatory mechanism(s) governing PIAS3 expression in MM remain unclear. Here, we demonstrate that PIAS3 protein expression does not correlate with its mRNA level in MM cell lines, indicating that PIAS3 expression is regulated at a post-transcriptional level. Inhibition of proteasomal degradation with MG132 (10 μm) or bortezomib (1 μm), alone and in combination, did not increase PIAS3 protein levels; furthermore, inhibition of protein synthesis by cycloheximide treatment did not decrease PIAS3 levels within 48 h, suggesting that PIAS3 expression is not actively regulated at a post-translational level. To determine whether miRNA (miRs) can translationally regulate PIAS3 expression, we combined miR microarray analysis with bioinformatic screening to identify candidate miRs, in MM cell lines with low PIAS3 expression, followed by luciferase reporter assays to validate miR regulation of the PIAS3 3'UTR. We identified miR-18a as a suppressor of PIAS3 expression that is upregulated in MM cells and whose inhibition can increase PIAS3 expression and suppress STAT3 activity. Moreover, we showed that miR-18a inhibition can decrease MM cell viability and that its expression is negatively correlated with MM patient survival. Taken together, these results suggest that targeting miR-18a may have therapeutic benefit in MM.
journal_name
Mol Oncoljournal_title
Molecular oncologyauthors
He T,McColl K,Sakre N,Chen Y,Wildey G,Dowlati Adoi
10.1002/1878-0261.12386subject
Has Abstractpub_date
2018-12-01 00:00:00pages
2124-2135issue
12eissn
1574-7891issn
1878-0261journal_volume
12pub_type
杂志文章abstract::The presence of circulating tumor cells (CTCs) in the blood of ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs with epithelial-mesenchymal-transition (EMT) or stem-like traits are supposed to be involved in metastatic progression and recurrence. Thus, investigating the tran...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.04.002
更新日期:2016-08-01 00:00:00
abstract::The abnormal expression of long noncoding RNAs (lncRNAs) is associated with human carcinoma. The present study aimed to investigate the mechanisms underlying the function of lncRNA AK002107 in the progression of hepatocellular carcinoma (HCC). The differential expression of lncRNAs between HCC and paired nontumor tiss...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12487
更新日期:2019-05-01 00:00:00
abstract::Gene and protein expression of programmed death-ligand 1 (PD-L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)-related g...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12654
更新日期:2020-05-01 00:00:00
abstract::Most solid tumors, including colorectal cancers, shed cell-free DNA (ctDNA) in the blood. ctDNA can be analyzed to generate molecular profiles which capture the heterogeneity of the disease more comprehensively then tumor tissue biopsies. This approach commonly called 'liquid biopsy' can be applied to monitor response...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.005
更新日期:2016-03-01 00:00:00
abstract:BACKGROUND:DNA methylation alterations are early events in tumorigenesis and important in the regulation of gene expression in cancer cells. Lung cancer patients have in general a poor prognosis, and a deeper insight into the epigenetic landscape in lung adenocarcinoma tumors and its prognostic implications is needed. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2015.10.021
更新日期:2016-02-01 00:00:00
abstract::C4.4A is a metastasis-associated molecule that functions appear to rely on associated alph6beta4 integrin. To corroborate the impact of the C4.4A-alpha6beta4 integrin association on metastasis formation, C4.4A was knocked-down in a highly metastatic rat pancreatic adenocarcinoma (ASML, ASML-C4.4Akd). Metastasis format...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.05.002
更新日期:2013-10-01 00:00:00
abstract::Glycosylation is the stepwise procedure of covalent attachment of oligosaccharide chains to proteins or lipids, and alterations in this process have been associated with malignant transformation. Simultaneous analysis of the expression of all glycan-related genes clearly gives the advantage of enabling a comprehensive...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2009.12.001
更新日期:2010-04-01 00:00:00
abstract::Chimeric inhibitors, which merge two drug pharmacophores in a single molecule have become a prominent approach for the design of novel anticancer compounds. Here, we examined animacroxam, which combines histone deacetylase (HDAC) inhibitory and cytoskeleton-interfering pharmacophores, in testicular germ cell tumors (T...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12582
更新日期:2019-12-01 00:00:00
abstract::JS-2 is a novel gene located at 5p15.2 and originally detected in primary oesophageal cancer. There is no study on the role of JS-2 in colorectal cancer. The aim of this study is to determine the gene copy number and expression of JS-2 in a large cohort of patients with colorectal tumours and correlate these to the cl...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2011.06.003
更新日期:2011-10-01 00:00:00
abstract::Enumeration and characterization of circulating tumor cells (CTC) hold the promise of a real time liquid biopsy. They are however present in a large background of hematopoietic cells making their isolation technically challenging. In 2004, the CellSearch system was introduced as the first and only FDA cleared method d...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2015.12.002
更新日期:2016-03-01 00:00:00
abstract::Hydrophobic neoantigens are more immunogenic because they are better presented by the major histocompatibility complex and better recognized by T cells. Tumor cells can evade the immune response by expressing checkpoints such as programmed death ligand 1. Checkpoint blockade reactivates immune recognition and can be e...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12748
更新日期:2020-08-01 00:00:00
abstract:PURPOSE:Lobular carcinoma in situ (LCIS) is both a risk indicator and non-obligate precursor of invasive lobular carcinoma (ILC). We sought to characterize the transcriptomic features of LCIS and ILC, with a focus on the identification of intrinsic molecular subtypes of LCIS and the changes involved in the progression ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.12.005
更新日期:2015-04-01 00:00:00
abstract::Natural products remain a significant source of anticancer chemotherapeutics. The search for targeted drugs for cancer treatment includes consideration of natural products, which may provide new opportunities for antitumor cytotoxicity as single agents or in combination therapy. We examined the association of molecula...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12849
更新日期:2020-11-09 00:00:00
abstract::The identification of novel antimetastatic therapeutic targets is necessary for improved treatment of patients with acquired BRAF inhibitor-resistant (BRAFi-R) melanoma, in whom metastasis is a major concern. Our present study focused on the identification of such targets to explore novel antimetastatic therapeutic op...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12433
更新日期:2019-02-01 00:00:00
abstract::In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to io...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12635
更新日期:2020-03-01 00:00:00
abstract::As a critical feature of the tumor microenvironment, hypoxia is known to be a potent inducer of tumor metastasis, and it has been proposed that the initial steps in metastasis involve epithelial-mesenchymal transition (EMT). The strong correlation among hypoxia, EMT, and metastasis suggests that integrative assessment...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12491
更新日期:2019-07-01 00:00:00
abstract::Genetic and lifestyle/environmental factors are implicated in the aetiology of breast cancer. This review summarizes the current state of knowledge on rare high penetrance mutations, as well as moderate and low-penetrance genetic variants implicated in breast cancer aetiology. We summarize recent discoveries from larg...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2010.04.011
更新日期:2010-06-01 00:00:00
abstract::SMURF2 is a member of the HECT family of E3 ubiquitin ligases that have important roles as a negative regulator of transforming growth factor-β (TGF-β) signaling through ubiquitin-mediated degradation of TGF-β receptor I. However, the regulatory mechanism of SMURF2 is largely unknown. In this study, we identified that...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12581
更新日期:2019-12-01 00:00:00
abstract::Amplification of 3q26.2, found in many cancer lineages, is a frequent and early event in ovarian cancer. We previously defined the most frequent region of copy number increase at 3q26.2 to EVI1 (ecotropic viral integration site-1) and MDS1 (myelodysplastic syndrome 1) (aka MECOM), an observation recently confirmed by ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.02.008
更新日期:2013-06-01 00:00:00
abstract::Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1 or APE1) is a multifunctional protein that regulates numerous transcription factors associated with cancer-related pathways. Because APE1 is essential for cell viability, generation of APE1-knockout cell lines and determining a comprehensive list of genes...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12138
更新日期:2017-12-01 00:00:00
abstract::Near infrared photoimmunotherapy (NIR-PIT) is a new, highly-selective cancer theranostics that employs an antibody-photo absorber conjugate (APC). NIR-PIT has successfully treated preclinical tumor models with APCs and is now in the first-in-human phase 1 clinical trial for head and neck cancer patients against EGFR. ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2016.07.010
更新日期:2016-11-01 00:00:00
abstract::In our previous study, we identified 1241 loci with somatic copy number alterations in human hepatocellular carcinoma (HCC) using Affymetrix SNP 6.0 arrays, and a putative cancer gene SERPINA5 was uncovered in a novel chromosomal region with recurrent copy number loss at 14q31.1-32.13. The SERPINA5 was reported to be ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2013.12.003
更新日期:2014-03-01 00:00:00
abstract::CDC25 (cell division cycle 25) phosphatases are essential for cell cycle control under normal conditions and in response to DNA damage. They are represented by three isoforms, CDC25A, B and C, each of them being submitted to an alternative splicing mechanism. Alternative splicing of many genes is affected in response ...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2012.06.003
更新日期:2012-10-01 00:00:00
abstract::The interferon-inducible transcription factor STAT1 is a tumor suppressor in various malignancies. We investigated sex-specific STAT1 functions in colitis and colitis-associated colorectal cancer (CRC) using mice with specific STAT1 deletion in intestinal epithelial cells (STAT1∆IEC ). Male but not female STAT1∆IEC mi...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12178
更新日期:2018-04-01 00:00:00
abstract::The diversity of breast cancers reflects variations in underlying biology and affects the clinical implications for patients. Gene expression studies have identified five major subtypes- Luminal A, Luminal B, basal-like, ErbB2+ and Normal-Like. We set out to determine the role of DNA methylation in subtypes by perform...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2010.11.002
更新日期:2011-02-01 00:00:00
abstract::The promise of 'personalized cancer care' with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given tumor-type from patient to patient (inter-patient heterogeneity), and within an individual (intra-patient heterogeneity) as demon...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2014.09.011
更新日期:2015-05-01 00:00:00
abstract::Pharmacogenomics is the study of genetic factors determining drug response or toxicity. The use of pharmacogenomics is especially desirable in oncology because the therapeutic index of oncology drugs is often narrow, the need for favorable drug response is often acute, and the consequences of drug toxicity can be life...
journal_title:Molecular oncology
pub_type: 杂志文章,评审
doi:10.1016/j.molonc.2012.01.005
更新日期:2012-04-01 00:00:00
abstract::Transient receptor potential melastatin-4 channel (TRPM4) dysregulation contributes to heart conditions, immune diseases, and cervical and prostate cancer. Up to now, the involvement of TRPM4 in colorectal cancer (CRC) pathophysiology remains unknown. Here, we investigated tumor tissue microarrays from 379 CRC patient...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12566
更新日期:2019-11-01 00:00:00
abstract::Circulating tumor cell (CTC) analysis holds great potential to be a noninvasive solution for clinical cancer management. A complete workflow that combined CTC detection and single-cell molecular analysis is required. We developed the ChimeraX® -i120 platform to facilitate negative enrichment, immunofluorescent labelin...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1002/1878-0261.12876
更新日期:2020-12-10 00:00:00
abstract:PURPOSE:To compare the distribution and prognostic effect of the breast cancer molecular subtypes in young and elderly breast cancer patients. PATIENTS AND METHODS:Our study population (n = 822) consisted of all early breast cancer patients primarily treated with surgery in our center between 1985 and 1996. A total of...
journal_title:Molecular oncology
pub_type: 杂志文章
doi:10.1016/j.molonc.2014.03.022
更新日期:2014-07-01 00:00:00