•STIL is upregulated in breast cancer, and promoted the proliferation, migration and invasion of triple negative breast cancer.•Our findings, for the first time, provide novel insights into the ...regulatory role of STIL in the FA pathway within breast cancer.•Our findings identify STIL as a critical promoter of breast cancer progression by interacting with KLF16 to regulate FANCD2.
STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear.
We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed.
Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2.
Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.
STIL is significant overexpression in triple-negative breast cancer. And STIL interacts with KLF16 protein, thereby facilitating the binding of KLF16 to the FANCD2 promoter and promoting transcriptional activation of FANCD2 Display omitted
Öğrenci öğrenme stillerinin çeşitliliğinin yanısıra öğrenmenin yapılandırmacı doğasının artan tanınırlığı ile birlikte öğretmenlerin farklı öğretim stilleri kullanma ihtiyacı vurgulanır iken ...öğretmenlerin çeşitli öğretim stillerini ve algılaması hakkında çok az şey bilinmektedir. Buna paralel olarak antrenörlerin öğretim stilleri kullanması ve algılaması hakkında çok daha az çalışmanın olduğu görülmektedir. Bu nedenle, bu çalışmada antrenörlerin ve beden eğitimi öğretmenlerinin öğretim stillerini kullanma düzeyleri ve stillere ilişkin değer algılarının, grup, cinsiyet, yaş, eğitim durumları değişkenlerine göre karşılaştırarak incelenmiştir. Edirne merkezde MEM’de çalışan 90 öğretmen ile GSİM’de çalışan 39 antrenör olmak üzere toplam 129 katılımcı, kolayda örneklem yöntemi ile seçilmiş ve gönüllük ilkesine göre katılmışlardır. Bulgulara göre en çok değer verilen stiller, komut ve alıştırma, en az değer verilen stiller ise kendi kendine öğretme ve öğrencinin başlatması olarak sıralanmıştır. En çok kullanılan stiller komut ve alıştırma, en az kullanılan stiller ise kendi kendine öğretme ve öğrencinin başlatması olarak sıralandığı görülmektedir. Stillerin öğrencilere “Eğlenme”, “Öğrenme” ve “Motivasyon” sağlama boyutlarında; motivasyon açısından komut, alıştırma ve eşli çalışma, öğrenme açısından komut, alıştırma ve katılım, eğlence açısından komut, alıştırma ve katılım stillerine en fazla değer verildiği görülmektedir. Bulgular grup, cinsiyet ve yaş değişkenlerine göre stillere ilişkin değer algıları ve kullandıkları öğretim stilleri ortalama puanlarının karşılaştırılması sonuçlarında anlamlı değişikler olduğu görülmüştür. Sonuç olarak, en çok kullanılan ve değer verilen stiller olarak komut ve alıştırma stillerinin seçilmesi, öğretmen ve antrenörün öğrenciler üzerinde kontrolün daha fazla arttırma istekleri, bu stillere yönelten temel sebep olarak görülebilir. Bu nedenle beden eğitimi öğretmenliği ve antrenörlük programında öğrenimlerini sürdüren öğretmen ve antrenör adaylarının öğrenim süreleri boyunca aldıkları farklı derslerde uygulama imkanı bulmaları için fırsatlar verilerek, diğer öğretim stillerinin stratejik kullanım alanlarının keşfetmeleri sağlanarak, deneyim kazanmaları ve mesleki gelişim programlarının bu doğrultuda hazırlanması önerilir.
In this article, we present current stylometric studies on Delta. (1) We discuss why the use of cosine similarity improves the rate of success; our experiments on vector normalization lead to a ...better understanding of how Delta works. (2) Based on a corpus of Middle High German texts, we show that metrical properties can also be used for authorship attribution. The degree to which Delta is influenced by non-normalized medieval spellings is also investigated. (3) Using a corpus of Arabic-Latin translations, we explore how selective feature elimination can be used to separate the translator signal from the genre signal.
STIL centriolar assembly protein (STIL) is a cytoplasmic protein implicated in cellular growth and proliferation as well as chromosomal stability, which abnormal condition affected tumor immunity and ...tumor progression. However, the role of STIL in the biological mechanism of hepatocellular carcinoma (HCC) remains unclear.
Comprehensive bioinformatic approaches, in vitro functional assays, and validation were conducted to elucidate the oncogenic value of STIL in HCC.
In the present study, we found that STIL may serve as an independent prognostic indicator and a potential oncogene in HCC. Gene set enrichment analysis (GSEA), and Gene set variation analysis (GSVA) showed that upregulated expression of STIL was positively associated with pathways enriched in the cell cycle and DNA damage response. Subsequently, we identified several non-coding RNAs (ncRNAs) accounting for the upregulation of STIL expression using a combination of in silico bioinformatics approaches (including expression analysis, correlation analysis, and survival analysis). Finally, CCNT2-AS1/SNHG1-has-miR-204-5p-STIL axis was screened out as the most potential upstream ncRNA-related pathway of STIL in HCC. Moreover, STIL expression is highly associated with the infiltration of immune cells, the expression of immune checkpoints, as well as the survival benefit of immunotherapy/chemotherapy.
Our study discloses that ncRNAs-mediated overexpression of STIL independently predicted poor prognosis and correlated with the efficacy of PD-1-targeted immunotherapy in HCC.
A new critical method for the Divine Comedy which focuses not only on language-as-writing but also and equally on other discursive modes that the Divine Comedy authorizes. Multimodality was already ...present in Dante's time, and the reception of the Divine Comedy took place multimodally. Thus, a theoretical study of multimodality carried out under the semiotic lens sheds light on how and why a mode is more effective than another and/or how they may combine in producing signification and new ontologies warranted by Dante's text. Also, we do not yet have a critical theory that allows us to understand the function of multimodality for the creation of new forms of signification and of clarifying the ontological boundaries set forth by different modalities. It is a new and original study which contributes to the advancement of Dante Studies, Literary Criticism (with a focus on literary semiotics), Multimedia/Multiliteracy, philosophy of language, communication, and education.
Cartwheel assembly is considered the first step in the initiation of procentriole biogenesis; however, the reason for persistence of the assembled human cartwheel structure from S phase to late ...mitosis remains unclear. Here, we demonstrate mainly using cell synchronization, RNA interference, immunofluorescence and time-lapse-microscopy, biochemical analysis, and methods that the cartwheel persistently assembles and maintains centriole engagement and centrosome integrity during S phase to late G2 phase. Blockade of the continuous accumulation of centriolar Sas-6, a major cartwheel protein, after procentriole formation induces premature centriole disengagement and disrupts pericentriolar matrix integrity. Additionally, we determined that during mitosis, CDK1-cyclin B phosphorylates Sas-6 at T495 and S510, disrupting its binding to cartwheel component STIL and pericentriolar component Nedd1 and promoting cartwheel disassembly and centriole disengagement. Perturbation of this phosphorylation maintains the accumulation of centriolar Sas-6 and retains centriole engagement during mitotic exit, which results in the inhibition of centriole reduplication. Collectively, these data demonstrate that persistent cartwheel assembly after procentriole formation maintains centriole engagement and that this configuration is relieved through phosphorylation of Sas-6 by CDK1-cyclin B during mitosis in human cells.
Colorectal cancer (CRC) is one of the most common cancers worldwide, and emerging lines of evidence have implicated circular RNAs (circRNAs), a novel class of endogenous noncoding RNAs, in CRC ...development. However, whether plasma circRNAs might be novel diagnostic biomarkers for CRC remains unclear.
We investigated the plasma levels of selected circRNAs by quantitative real-time PCR (qRT-PCR). The presence of the candidate circRNAs was confirmed through RNase R assays, qRT-PCR and DNA sequencing, and their diagnostic value was evaluated using a receiver operating characteristic (ROC) curve.
The plasma levels of three circRNAs (circ-CCDC66, circ-ABCC1 and circ-STIL) were significantly decreased in CRC patients (n = 45) compared with healthy controls (n = 61). The ROC curve analysis showed that the area under the ROC curve (AUC) of the three-circRNA panel was 0.780, which is higher than that of traditional protein biomarkers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19–9 (CA19-9). Combining the circRNA panel with CEA and CA19-9 might improve the ability to diagnose CRC (AUC = 0.855). In addition, the plasma circ-ABCC1 level was related to tumor growth and progression, and the plasma circ-CCDC66 and circ-ABCC1 levels were decreased in precursor lesions of CRC, including colon adenomas and adenomatous polyps. More importantly, circ-CCDC66 and circ-STIL were found to be useful for diagnosing early-stage CRC, and the three-circRNA panel improved the ability to diagnose CEA-negative and CA19-9-negative CRC.
Our study provides the first identification of a panel of three plasma circRNAs that could serve as a novel and independent diagnostic biomarker for CRC.
The number of centrioles is tightly controlled to ensure bipolar spindle assembly, which is a prerequisite to maintain genome integrity. However, our understanding of the fundamental principle that ...governs the formation of a single procentriole per parental centriole is incomplete. Here, we show that the local restriction of Plk4, a master regulator of the procentriole formation, is achieved by a bimodal interaction of STIL with Plk4. We demonstrate that the conserved short coiled-coil region of STIL binds to and protects Plk4 from protein degradation at the site of procentriole formation. On the other hand, the conserved C-terminal region of STIL named truncated in microcephaly (TIM) domain promotes autophosphorylation and degradation of adjacent Plk4 by the direct interaction. Thus, we propose that positive and negative regulation based on the bimodal binding of Plk4 and STIL ensures the formation of a single procentriole per parental centriole.
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•Plk4 asymmetry is achieved prior to procentriole formation•Autophosphorylation of Plk4 is critical for the restriction of Plk4 at a single site•Bimodal binding of STIL to Plk4 regulates the activation and degradation of Plk4•The TIM domain of STIL limits Plk4 at centrioles and the number of procentrioles
Ohta et al. show that Plk4 asymmetrically localizes around mother centrioles before the onset of procentriole formation. Furthermore, they reveal that bimodal binding of STIL to Plk4 restricts Plk4 localization at a single site and thus ensures formation of a single procentriole per mother centriole.
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