tbuckley/cabot-search huggingface dataset:
Glucocorticoid Dosages and Acute‐Phase Reactant Levels at Giant Cell Arteritis Flare in a Randomized Trial of Tocilizumab
Authors: John H. Stone, Katie Tuckwell, Sophie Dimonaco, Micki Klearman, Martin Aringer, Daniel Blockmans, Elisabeth Brouwer, Maria C. Cid, Bhaskar Dasgupta, Juergen Rech, Carlo Salvarani, Hendrik Schulze‐Koops, Georg Schett, Robert Spiera, Sebastian H. Unizony, Neil Collinson
Journal: Arthritis & Rheumatology (2019)

This study was undertaken to evaluate glucocorticoid dosages and serologic findings in patients with giant cell arteritis (GCA) flares.Patients with GCA were randomly assigned to receive double-blind dosing with either subcutaneous tocilizumab (TCZ) 162 mg weekly plus 26-week prednisone taper (TCZ-QW + Pred-26), every-other-week TCZ plus 26-week prednisone taper (TCZ-Q2W + Pred-26), placebo plus 26-week prednisone taper (PBO + Pred-26), or placebo plus 52-week prednisone taper (PBO + Pred-52). Outcome measures were prednisone dosage, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR) at the time of flare.One hundred patients received TCZ-QW + Pred-26, 49 received TCZ-Q2W + Pred-26, 50 received PBO + Pred-26, and 51 received PBO + Pred-52. Of the 149 TCZ-treated patients, 36 (24%) experienced flare, 23 (64%) of whom were still receiving prednisone (median dosage 2.0 mg/day). Among 101 PBO + Pred-treated patients, 59 (58%) experienced flare, 45 (76%) of whom were receiving prednisone (median dosage 5.0 mg/day). Many flares occurred while patients were taking >10 mg/day prednisone: 9 (25%) in the TCZ groups and 13 (22%) in the placebo groups. Thirty-three flares (92%) in TCZ-treated groups and 20 (34%) in PBO + Pred-treated groups occurred with normal CRP levels. More than half of the PBO + Pred-treated patients had elevated CRP levels without flares. Benefits of the TCZ and prednisone combination over prednisone alone for remission induction were apparent by 8 weeks.Most GCA flares occurred while patients were still receiving prednisone. Acute-phase reactant levels were not reliable indicators of flare in patients treated with TCZ plus prednisone or with prednisone alone. The addition of TCZ to prednisone facilitates earlier GCA control.
PREDICTORS OF IN-HOSPITAL MORTALITY AMONG 17,034 PATIENTS WITH MYOCARDITIS: INSIGHTS FROM THE NATIONWIDE INPATIENT SAMPLE
Authors: Barbara Anna Danek, Aris Karatasakis, Adamantios Tsangaris, Monali Patel, Shuaib Abdullah, Subhash Banerjee, Emmanouil Brilakis
Journal: Journal of the American College of Cardiology (2019)
REMOTE PATIENT MONITORING WITH A NOVEL DIGITAL MEDICINE PROGRAM PROVIDES OBJECTIVE CLINICAL DATA TO OPTIMIZE OUTCOMES AND PREVENT UNNECESSARY HEALTHCARE RESOURCE UTILIZATION
Authors: Mohamad Hemu, Joanne Michelle D. Gomez, Amanda Tosto, Neelum T. Aggarwal, Anupama Rao, Anthony J. Perry, Annabelle S. Volgman
Journal: Journal of the American College of Cardiology (2019)
Iron oxide nanoparticles promote macrophage autophagy and inflammatory response through activation of toll-like Receptor-4 signaling
Authors: Rongrong Jin, Li Liu, Wencheng Zhu, Danyang Li, Li Yang, Jimei Duan, Zhongyuan Cai, Yu Nie, Yunjiao Zhang, Qiyong Gong, Bin Song, Longping Wen, James M. Anderson, Hua Ai
Journal: Biomaterials (2019)
PATTERN OF β-BLOCKER USE FOLLOWING HOSPITALIZATION OF OLDER ADULTS WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION (HFPEF) FROM THE REGARDS STUDY
Authors: Brian Yum, Alexi Archambault, Jerard Kneifati-Hayek, Ligong Chen, Emily Levitan, Mark Lachs, Mathew Maurer, Monika Safford, Parag Goyal
Journal: Journal of the American College of Cardiology (2019)
OPTICAL COHERENCE TOMOGRAPHY-DEFINED PLAQUE INSTABILITY ASSOCIATED WITH CORONARY FLOW CAPACITY CLASSIFIED WITH PRESSURE-TEMPERATURE SENSOR-TIPPED WIRE
Authors: Hiroaki Ohya, Eisuke Usui, Tomoki Horie, Haruhito Yuki, Hidenori Hirano, Yoshinori Kanno, Masahiro Hada, Yohei Sumino, Masao Yamaguchi, Masahiro Hoshino, Yoshihisa Kanaji, Akinori Sugano, Taishi Yonetsu, Tsunekazu Kakuta
Journal: Journal of the American College of Cardiology (2019)
IMPACT OF CARDIOVASCULAR RISK FACTORS ON SURVIVAL AFTER LIVER TRANSPLANTATION: RESULTS FROM A PROSPECTIVE BINATIONAL MULTICENTRE REGISTRY
Authors: Anoop Ninan Koshy, H.M. Omar Farouque, Jay Ramchand, Hui-Chen Han, Benjamin Cailes, Mandy Byrne, Adam Testro, Robert M. Jones, Jithin Sajeev, Han Lim, Peter W. Angus, David Clark, Matias B. Yudi, Paul J. Gow
Journal: Journal of the American College of Cardiology (2019)
ELEVATED PULMONARY VASCULAR RESISTANCE IS ASSOCIATED WITH LONG-TERM MORTALITY IN PULMONARY HYPERTENSION PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Ibrahim Sultan, Valentino Bianco, Miho Fukui, Dustin Kliner, Floyd Thoma, Joon Lee, John Schindler, Forozan Navid, Thomas Gleason, Joao L. Cavalcante
Journal: Journal of the American College of Cardiology (2019)
EPICARDIAL VENTRICULAR TACHYCARDIA ABLATION GUIDED BY A NOVEL HIGH-RESOLUTION CONTACT MAPPING SYSTEM: A MULTICENTRE STUDY
Authors: Rui Shi, Zhong Chen, Andrianos Kontogeorgis, Fred Sacher, Paolo Della Bella, Caterina Bisceglia, Ruairidh Martin, Christian Meyer, Stephan Willems, Vias Markides, Philippe Maury, Tom Wong
Journal: Journal of the American College of Cardiology (2019)
ASSESSMENT OF CORONARY ARTERY PLAQUE CHARACTERISTICS AND DISTRIBUTION IN PATIENTS OF SOUTH ASIAN DESCENT USING CORONARY COMPUTED TOMOGRAPHIC ANGIOGRAPHY
Authors: Neiman Ramjattan, Kishen Bulsara, Carlos Ceron, Kyla D'Angelo, Gagan Verma, Ofek Hai, Roman Zeltser, Amgad Makaryus
Journal: Journal of the American College of Cardiology (2019)
Combining Dasatinib and AC220 Reduces Stroma-Based pSTAT5Y694 in FLT3-ITD+ AML and Overcomes FLT3 TKI Resistance
Authors: Ami B. Patel, Anthony D. Pomicter, Dongqing Yan, Anna M. Eiring, Anca Franzini, Thomas O'Hare, Michael W. Deininger
Journal: Blood (2018)
Abstract 280: MCL-1 <sub>Matrix</sub> Promotes Mitochondrial Fusion and Protects Against TAC Induced Hypertrophy
Authors: Leonardo J Leon, Alexandra G Moyzis, Asa B Gustafsson
Journal: Circulation Research (2018)

The anti-apoptotic BCL-2 protein MCL-1 is highly expressed in the myocardium, and we have previously found that deletion in cardiomyocytes leads to mitochondrial dysfunction and rapid development of heart failure. MCL-1 exists both in the outer mitochondrial membrane (MCL-1 OM ) and in the mitochondrial matrix (MCL-1 Matrix ). Because Mcl-1 -/- mice lack both MCL-1 Matrix and MCL-1 OM , the functional role of each form remains unknown. While studies have implicated MCL-1 OM in regulating apoptosis, very little is known about the functional role of MCL-1 Matrix . Here, we show that mitochondria are responsive to alterations in cellular metabolism, and culturing mouse embryonic fibroblasts (MEFs) in “oxidative” media containing galactose or acetoacetate led to a significant increase in the MCL-1 Matrix /MCL-1 OM ratio and elongation of mitochondria. We confirmed that MCL-1 Matrix overexpression promoted mitochondrial fusion and reduced maximal mitochondrial respiration under baseline conditions. Interestingly, the elongated mitochondria were initially protected against FCCP-induced fission and mitophagy. However, prolonged exposure to FCCP resulted in abrogation of MCL-1 Matrix import. Accumulation of MCL-1 Matrix on the outer membrane led to its degradation and subsequent induction of mitophagy. Furthermore, to investigate its functional role in the heart, we generated cardiac specific MCL-1 Matrix (αMHC-MCL-1 Matrix ) transgenic mice. The mice show no differences in cardiac structure and function compared to wild-type litter mates at 3 months. However, ultrastructural analysis revealed the presence of enlarged mitochondria in myocytes from αMHC-MCL-1 Matrix mice. Finally, we subjected WT and αMHC-MCL-1 Matrix mice to transverse aortic constriction (TAC) and we found that αMHC-MCL-1 Matrix mice had reduced heart weight to body weight (HW/BW) ratio and decreased expression of hypertrophy markers ANF, BNP, and MHC-β at two weeks post-TAC compared to WT. Thus, our studies indicate that cardiac overexpression of MCL-1 Matrix promotes mitochondrial enlargement in myocytes and alleviates stress placed on the heart during pressure overload.
SHORT AND LONG-TERM OUTCOMES OF MEDICARE PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PERCUTANEOUS CORONARY INTERVENTION VIA THE TRANSRADIAL VERSUS TRANSFEMORAL APPROACH: INSIGHTS FROM THE WASHINGTON STATE CLINICAL OUTCOMES ASSESSMENT PROGRAM
Authors: Sean Bell, Akash Kataruka, Kathleen Kearney, Ravi Hira
Journal: Journal of the American College of Cardiology (2019)
Comparison of Overall Survival Associated with Lenalidomide+Dexamethasone and Bortezomib+Dexamethasone Among Relapsed/Refractory Multiple Myeloma Patients: A Matched Analysis of Real World and Clinical Trial Populations
Authors: Ajay Nooka, Peter M. Voorhees, Shaji K Kumar, Maneesha Mehra, Annette Lam, Mary Slavcev, Ravi Potluri, Anandaroop Dasgupta
Journal: Blood (2017)
RELATIONSHIP BETWEEN COMPONENTS OF DIET AND CARDIOVASCULAR DISEASE AND MORTALITY: AN OVERVIEW OF CURRENT EVIDENCE
Authors: Chun Shing Kwok, Martha Gulati, Erin Michos, Elizabeth P. Frates, Jessica Potts, Pensee Wu, Lorraine Watson, Yoon K. Loke, Christian D. Mallen, Mamas A. Mamas
Journal: Journal of the American College of Cardiology (2019)
ROLE OF GEOGRAPHIC LOCATION AND SOCIOECONOMIC STATUS IN THE OUTCOME OF PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR): A STATE-WIDE ANALYSIS
Authors: Chin Siang Ong, Joseph Canner, Lucy Nam, Roald Teuben, Jingnan Han, Stefano Schena
Journal: Journal of the American College of Cardiology (2019)
TREATMENT OF PERIODONTAL DISEASE SIGNIFICANTLY AFFECTS THE RATE OF CARDIOVASCULAR EVENTS IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Luis Henrique W. Gowdak, Marcela A. Santos-Paul, Ricardo S. Neves, Flavio de Paula, Luiz Bortolotto, Luiz Antonio M. Cesar, Jose Antonio F. Ramires, Elias David-Neto, Jose Lima
Journal: Journal of the American College of Cardiology (2019)
SLEEP OUTCOMES FROM AWAKE-HF, A RANDOMIZED CLINICAL TRIAL WITH OPEN-LABEL EXTENSION OF SACUBITRIL/VALSARTAN VERSUS ENALAPRIL IN PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION
Authors: Robert L. Owens, Kade Birkeland, J. Thomas Heywood, Steven Steinhubl, Jonas Dorn, Daniel Grant, Emmanuel Fombu, Kevin McCague, Raj Khandwalla
Journal: Journal of the American College of Cardiology (2019)
CPX-351 Exposure-Response Based on Cumulative Dose of Cytarabine and Daunorubicin in Patients with Newly Diagnosed, Treatment-Related Acute Myeloid Leukemia (AML) or AML with Myelodysplasia-Related Changes
Authors: Kamalika Banerjee, Qi Wang, Jing Wang, Jackie Gibbons
Journal: Blood (2017)
Immune Responses To Non-Typeable Haemophilus Influenzae In Protracted Bacterial Bronchitis
Authors: J. W. Upham, A. Chang, S. Pizzutto, M. Carroll, P. Gibson, J. Simpson, K. J. Baines, H. Petsky, S. Yerkovich, A. Chen
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
Abstract 585: CDK8 Activity-dependent Regulation of Heart Disease
Authors: Rachel Minerath, Allison Vaske, Duane Hall, Chad Grueter
Journal: Circulation Research (2018)

Pathological cardiac hypertrophy represents a major risk factor for heart failure (HF). The hypertrophic response is orchestrated in part through transcriptional alterations that ultimately modify cardiac function. Mediator is a multiprotein complex that coordinates signal dependent transcription factors with basal transcriptional machinery including RNA polymerase II and general transcription factors. Transcriptional regulation by Mediator complex can be modified by the association of the Mediator complex kinase submodule with the core complex. Cyclin-dependent kinase 8 (CDK8) is a kinase present in the submodule that has been demonstrated to have a complex role in transcriptional regulation through a number of mechanisms involving both transcriptional activation and inhibition. Our lab has demonstrated that CDK8 expression is upregulated in murine HF models as well as in failing human hearts. In addition, cardiac CDK8 over-expression promotes transcriptional remodeling that results in dilated cardiomyopathy suggesting that CDK8 inhibition may represent a novel pharmacological target. This study utilizes CDK8 kinase inhibitor, Senexin A, which is being evaluated as an anti-cancer chemotherapeutic agent. Here, we demonstrate that Senexin A inhibits kinase activity in an in vitro neonatal rat cardiomyocyte (NRCM) model resulting in reduced cardiomyocyte hypertrophy as well as a reduction in expression of specific cardiomyocyte hypertrophy markers. These studies demonstrate a role for CDK8 activity in transcriptional regulation of genes associated with pathological cardiac remodeling that drives cardiac hypertrophy and ultimately HF.
RIGHT VENTRICULAR OUTFLOW TRACT OBSTRUCTION IN AN ADULT WITH REPAIRED TETRALOGY OF FALLOT PRESENTING AS TET SPELLS
Authors: Rahul Singh, Miguel A. Chavez, Stephanie Fuentes Rojas, Akanksha Thakkar, Omar Tamimi, Thomas MacGillivray, C. Huie Lin
Journal: Journal of the American College of Cardiology (2019)
Proteomic approach to identify markers for invasive cervix cancer - A prospective pilot study.
Authors: David Mysona, Adam Pyrzak, Jennifer Allen, Ashok Sharma, Wenbo Zhi, Bunja Jane Rungruang, Sharad A. Ghamande, Jin-Xiong She
Journal: Journal of Clinical Oncology (2015)

e22257 Background: Cervical cancer is the second most common malignancy of women worldwide and a major cause of mortality in young women. In this prospective study, we attempted to identify a set of serum biomarkers, which could accurately identify patients who have invasive cervical cancer and help monitor disease status (recurrence and remission). Methods: A Luminex bead array was used to measure serum protein concentrations of an assortment of 19 different, promising proteins in patients with cervical cancer (n=23) compared to women with precancerous lesions (CIN2-3)(n=20), and patients with normal cervical cytology (n=20) in this IRB approved prospective study. Cervical cancer patients had blood samples taken starting from within 30 days of their diagnosis or surgery date and included both squamous cell and adenocarcinomas. They had repeat blood samples taken on follow up visits after completing therapy. These results were correlated to clinical data. Results: CIN and controls have very similar levels of serum proteins although CIN may have increased levels of MMP7 and sICAM1. Five proteins (OPG, CEA, CA199, IGFBP7, and IGFBP4) had significantly different levels in cervical cancer patients compared to both controls and CIN (p < 0.05) with Area Under the Curve values of 0.761, 0.758, 0.68, 0.83 and 0.862 respectively. IGBP7 had a sensitivity of 58% at 95% specificity. IGBP4 had a sensitivity of 75% and 95% specificity for correctly identifying invasive disease. Conclusions: Several serum proteins are significantly altered in cervical cancer patients compared to both controls and CIN, and are worth studying further for clinical utility. Area Under the Curve (Confidence Interval) P-value Sensitivity at 95% Specificity IGFBP4 0.86 ( 0.82 - 0.9 ) 9.64E-09 75 IGFBP7 0.83 ( 0.79 - 0.87 ) 1.27E-07 55.32 OPG 0.76 ( 0.71 - 0.81 ) 3.21E-05 34.78 CEA 0.76 ( 0.71 - 0.81 ) 3.61E-05 40.43 CA153 0.74 ( 0.69 - 0.79 ) 1.22E-04 8.51
CHANGES IN DIGOXIN AND ANGIOTENSIN CONVERTING ENZYME INHIBITOR (ACEI) USE IN INFANTS WITH SINGLE VENTRICLE (SV) PHYSIOLOGY FOLLOWING LANDMARK PUBLICATIONS
Authors: Derek Weyhrauch, Nelangi Pinto, Dongngan T. Truong, Venugopal Amula, Linda Lambert, Chong Zhang, Angela Presson, Jacob Wilkes, L. LuAnn Minich, Richard Williams
Journal: Journal of the American College of Cardiology (2019)
THE ASSOCIATION OF PREOPERATIVE CHARACTERISTICS WITH THE REINTERVENTION RISK IN PATIENTS UNDERGOING REVASCULARIZATION FOR CRITICAL LIMB ISCHEMIA
Authors: Osamu Iida, Mitsuyoshi Takahara, Yoshimitsu Soga, Akio Kodama, Hiroto Terashi, Toshiaki Mano, Nobuyoshi Azuma
Journal: Journal of the American College of Cardiology (2019)
Functional reconstitution of BRCA1 gene product modifies proteomic profile and sensitivity of HCC1937 breast cancer cells to mitotic spindle interfering agents
Authors: Pierosandro Tagliaferri, Giovanni Cuda, Simona Blotta, Rita Casadonte, Barbara Quaresima, Camillo Palmieri, Pierfrancesco Tassone, Rosa Terracciano, Maria Saveria Rotundo, Francesco Costanzo, Salvatore Venuta
Journal: Cancer Research (2004)

4751  Germ-line mutations in BRCA1/2 genes account for most of hereditary breast and ovarian cancers. Gene expression profiling studies have disclosed a specific molecular signature for BRCA1/2 breast tumors as compared to sporadic cases. We have recently reported that HCC1937 human cell line, derived from a breast cancer arising in BRCA1 setting, showes a peculiar chemosensitivity profile if compared to sporadic breast tumor-derived cell lines (MCF-7, MDAMB-231). This particular response is, however, completely reverted by reconstituted expression of the wild type BRCA1 gene function following transfection of a full length BRCA1 cDNA. We have investigated the sensitivity to microtubule interfering agents in this experimental model. HCC1937 cells are relatively sensitive to vinorelbine (IC:50 2.5 μM) and resistant to taxol (IC:50 >2 μMol). Reconstituted expression of wild type BRCA1 in three distinct HCC1937 BRCA1WT clones led to reduced sensitivity to vinorelbine (IC:50 20 μM) and enhanced response to taxol (0.4 μM). In order to assess the impact of the BRCA1 gene product on cell sensitivity to mitotic spindle interfering agents, we have investigated BRCA1 targeting to mitotic spindle in HCC1937 cells as well as in the reconstituted cell line by confocal microscopy. Interestingly, in both cell lines the BRCA1 protein was able to target the mitotic spindle and colocalized with alpha-tubulin. Moreover, we have performed a proteomic analysis on wild type and reconstituted HCC1937 cell lines. LC-MS/MS analysis of ICAT-treated cells showed important changes in the expression levels of different proteins, therefore identifying specific profiles. In particular, heat shock proteins HSP-90 and HSP-70 were significantly overexpressed in wild type HCC1937. This observation appears of interest taking in account the recent finding of increased sensitivity to taxol following inactivation of HSP-90. We hypothesize that the differential sensitivity to microtubule interfering agents disclosed by HCC1937 cells and derivative clones is not due to a failure of the mutated BRCA1 gene product to target the mitotic spindle, but it might be related to substantial changes in the whole cell proteome with enhanced expression of proteins like HSPs which are involved in the sensitivity profile to this class of anticancer compounds.
OUTCOMES OF CAROTID ARTERY STENTING VERSUS CAROTID ARTERY ENDARTERECTOMY IN PATIENTS UNDERGOING ELECTIVE CAROTID ARTERY REVASCULARIZATION: A PROPENSITY MATCHED ANALYSIS FROM THE NATIONAL INPATIENT SAMPLE
Authors: Setri Fugar, Alexis Okoh, Alfred Solomon, Ebru Ozturk, Devanji Dave, Marie-France Poulin, Annabelle Volgman
Journal: Journal of the American College of Cardiology (2019)
THE IMPACT OF MITRAL REGURGITATION ON MORTALITY AND HEART FAILURE ADMISSIONS IN NEWLY DIAGNOSED HEART FAILURE PATIENTS
Authors: David Patrick Cork, Hirsch Mehta, Colin Barker, Patrick Verta, Michael P. Ryan, Erin Baker, Candace Gunnarsson, Sarah Mollenkopf, Joanna Van Houten, Peter McCullough
Journal: Journal of the American College of Cardiology (2019)
OUTCOMES OF MICRA LEADLESS PACEMAKER IMPLANTATION WITH UNINTERRUPTED ANTICOAGULATION
Authors: Soroosh Kiani, George Black, Birju Rao, Nancy Thakkar, Christopher Massad, Patel Akshar, Faisal Merchant, Michael Hoskins, David Delurgio, Anshul Patel, Anand Shah, Angel Leon, Stacy Westerman, Michael Lloyd, Mikhael El Chami
Journal: Journal of the American College of Cardiology (2019)
The histone methyltransferase EZH2 primes the early differentiation of follicular helper T cells during acute viral infection
Authors: Xiangyu Chen, Guoshuai Cao, Jialin Wu, Xinxin Wang, Zhiwei Pan, Jianbao Gao, Qin Tian, Lifan Xu, Zhirong Li, Yaxing Hao, Qizhao Huang, Pengcheng Wang, Minglu Xiao, Luoyingzi Xie, Shupei Tang, Zhenyu Liu, Li Hu, Jianfang Tang, Ran He, Li Wang, Xinyuan Zhou, Yuzhang Wu, Mengjie Chen, Beicheng Sun, Bo Zhu, Jun Huang, Lilin Ye
Journal: Cellular and Molecular Immunology (2019)

Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. However, whether and how EZH2 regulates follicular helper T (TFH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific TFH cells compared to those in TH1 cells. Ablation of EZH2 in LCMV-specific CD4+ T cells leads to a selective impairment of early TFH cell fate commitment, but not late TFH differentiation or memory TFH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for TFH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs TFH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early TFH differentiation during acute viral infection.
circKIF4A acts as a prognostic factor and mediator to regulate the progression of triple-negative breast cancer
Authors: Hailin Tang, Xiaojia Huang, Jin Wang, Lu Yang, Yanan Kong, Guanfeng Gao, Lijuan Zhang, Zhe-Sheng Chen, Xiaoming Xie
Journal: Molecular Cancer (2019)

Increasing studies has found that circular RNAs (circRNAs) play vital roles in cancer progression. But the expression profile and function of circRNAs in triple-negative breast cancer (TNBC) are unclear. We used a circRNA microarray to explore the circRNA expression profile of TNBC. The expression of the top upregulated circRNA, circKIF4A, was confirmed by qRT-PCR in breast cancer cell lines and tissues. Kaplan-Meier survival analysis was conducted to analyze the clinical impact of circKIF4A on TNBC. A series of experiments was performed to explore the functions of circKIF4A in TNBC progression, such as cell proliferation and migration. We investigated the regulatory effect of circKIF4A on miRNA and its target genes to explore the potential regulatory mechanisms of circKIF4A in TNBC. qRT-PCR analyses verified that circKIF4A was significantly upregulated and positively associated with poorer survival of TNBC. The inhibition of circKIF4A suppressed cell proliferation and migration in TNBC. Luciferase reporter assay and RNA immunoprecipitation assay revealed that circKIF4A and KIF4A could bind to miR-375 and that circKIF4A regulated the expression of KIF4A via sponging miR-375. The circKIF4A-miR-375-KIF4A axis regulates TNBC progression via the competitive endogenous RNA (ceRNA) mechanism. circKIF4A may therefore serve as a prognostic biomarker and therapeutic target for TNBC.