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Ran Tao, Baotong Zhang, Yixiang Li, Jamie L King, Ruoyu Tian, Siyuan Xia, Cara Rae Schiavon, Jin-Tang Dong
Krüppel-like factor 5 (KLF5) is a basic transcription factor that regulates diverse cellular processes during tumor development. Acetylation of KLF5 at lysine 369 (K369) reverses its function from promoting to suppressing cell proliferation and tumor growth. In this study, we examined the regulation of KLF5 by histone deacetylases in the prostate cancer cell line DU 145. While confirming the functions of HDAC1/2 in KLF5 deacetylation and the promotion of cell proliferation, we found that the knockdown of HDAC1/2 upregulated KLF5 protein but not KLF5 mRNA, and the increase in KLF5 protein level by silencing HDAC1/2 was at least in part due to decreased proteasomal degradation...
April 18, 2018: Biochemical and Biophysical Research Communications
Vivek Shukla, Mahadev Rao, Hongen Zhang, Jeanette Beers, Darawalee Wangsa, Danny Wangsa, Floryne O Buishand, Yonghong Wang, Zhiya Yu, Holly Stevenson, Emily Reardon, Kaitlin C McLoughlin, Andrew Kaufman, Eden Payabyab, Julie A Hong, Mary Zhang, Sean R Davis, Daniel C Edelman, Guokai Chen, Markku Miettinen, Nicholas Restifo, Thomas Ried, Paul S Meltzer, David S Schrump
RATIONALE: Despite extensive studies, the genetic and epigenetic mechanisms that mediate initiation and progression of lung cancers have not been fully elucidated. Previously, we have demonstrated that via complementary mechanisms, including DNA methylation, polycomb repressive complexes, and noncoding RNAs, cigarette smoke induces stem-like phenotypes that coincide with progression to malignancy in normal respiratory epithelia as well as enhanced growth and metastatic potential of lung cancer cells...
April 2018: Annals of the American Thoracic Society
Mingyue Liu, Xiqing Li, Ke-Zheng Peng, Tianhui Gao, Yao Cui, Ning Ma, Yun Zhou, Guiqin Hou
Kruppel-like factor 4 (Klf4) was reported to have both tumor suppressive and oncogenic roles on tumorigenesis, which is depend on its subcellular localization. In this study, the expression and subcellular localization of Klf4 in non-small cell lung cancer (NSCLC) patients as well as its clinical significance were analyzed, and the expression and subcellular localization of Klf4 in A549 cells and A549/DDP cells were detected. The results showed that the expression of Klf4 in nucleus was related to the histological grade and clinical stage of NSCLC patients...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Qidong Jiang, Changxue Wu, Qiong Zhang
OBJECTIVE: To investigate whether microRNA-34a (miR-34a) participates in lipopolysaccharide (LPS) mediated sepsis related renal function impairment via Kruppel-like factor 4 (KLF4). METHODS: Thirty healthy male Sprague-Dawley (SD) rats, weighing 180-200 g, were randomly divided into two groups: control group and model group, with 15 rats in each group. The SD rats from model group were injected with LPS 7.5 mg/kg to induce sepsis related renal function impairment model, the SD rats from control group were injected with normal saline...
April 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Shuchen Li, Chujiao Lin, Jie Zhang, Huangheng Tao, Huan Liu, Guohua Yuan, Zhi Chen
Odontoblastic differentiation of human dental pulp stem cells (hDPSCs) is essential for the formation of reparative dentin after dental caries or injury. Our previous studies have demonstrated that krüppel-like factor 4 (KLF4) is a critical transcription factor that promotes the odontoblastic differentiation of hDPSCs. Analysis of the microRNA binding sites within the 3'-UTR of KLF4 revealed that QKI, an RNA-binding protein, shared the most microRNAs with KLF4, presumably served as a "competent endogenous RNA (ceRNA)" with KLF4...
April 16, 2018: Journal of Cellular Physiology
Hao Liang, Huiping Sun, Jinfeng Yang, Chun Yi
MicroRNAs (miRs) are important in hepatocellular carcinoma (HCC) progression. miR‑145‑5p acts as a tumor suppressor in certain malignancies, however, its role in HCC remains unclear. The present study aimed to perform a functional analysis of miR‑145‑5p in HCC in order to elucidate its role in the pathogenesis of HCC. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) was performed to analyze tissue and cellular expression of miR‑145‑5p in HCC. Following miRNA mimics transfection, cell viability, apoptosis and cells migration were determined by Cell Counting kit‑8, Annexin V‑FITC/propidium iodide staining and Transwell analyses...
April 13, 2018: Molecular Medicine Reports
Francesco Bertoni, Davide Rossi, Emanuele Zucca
There are three different marginal zone lymphomas (MZLs): the extranodal MZL of mucosa-associated lymphoid tissue (MALT) type (MALT lymphoma), the splenic MZL, and the nodal MZL. The three MZLs share common lesions and deregulated pathways but also present specific alterations that can be used for their differential diagnosis. Although trisomies of chromosomes 3 and 18, deletions at 6q23, deregulation of nuclear factor kappa B, and chromatin remodeling genes are frequent events in all of them, the three MZLs differ in the presence of recurrent translocations, mutations affecting the NOTCH pathway, and the transcription factor Kruppel like factor 2 ( KLF2) or the receptor-type protein tyrosine phosphatase delta ( PTPRD )...
2018: F1000Research
Wei Feng, Qianyi Xie, Suo Liu, Ying Ji, Chunyun Li, Chunle Wang, Longyu Jin
Gefitinib have been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells...
April 6, 2018: Cancer Science
Peiyu Ji, Xin Fan, Xiaoyan Ma, Xuqing Wang, Jianxin Zhang, Zhengfa Mao
Krüppel-like factor 9 (KLF9) has been implicated in mediating a diverse range of biological processes. However, the expression pattern and biological functions of KLF9 in pancreatic ductal adenocarcinoma (PDAC) are still unknown. Here, we evaluated the role of KLF9 in pancreatic ductal adenocarcinoma (PDAC). Overexpression of KLF9 significantly inhibited proliferation and clone formation in PDAC cells, while silencing KLF9 expression dramatically promoted this effect in vitro. Knocking down the expression of KLF9 also promoted the tumorigenesis in the PDAC mouse xneograft model...
April 2, 2018: Biochemical and Biophysical Research Communications
Lijian Tong, Guoxian Qi
The phenotypic switch of vascular smooth muscle cells (VSMCs) is a major initiating factor for atherosclerotic cardiovascular diseases. Platelet‑derived growth factor‑BB (PDGF‑BB) initiates a number of biological processes that contribute to VSMC proliferation and phenotypic switch. Crocin, a component of saffron, has been reported to inhibit atheromatous plaque formation. However, the effects of crocin on PDGF‑BB‑induced VSMC proliferation and phenotypic switch remain unclear. The aim of the present study was to investigate the role of crocin on PDGF‑BB‑induced VSMCs proliferation and phenotypic switch and its underlying mechanisms...
April 5, 2018: Molecular Medicine Reports
Yanfeng Song, Ying Liu, Xiaowei Chen
PURPOSE: Parkinson's disease (PD) is a common age-dependent neurodegenerative disease. MiR-212 has been demonstrated to exert protective effects in several neurological disorders. The present study aimed to investigate the role and underlying molecular mechanism of miR-212 in PD. MATERIALS AND METHODS: 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cells were applied as a PD model in vitro. RT-qPCR was used to measure the expression of miR-212 and Kruppel-like factor 4 (KLF4) mRNA...
May 2018: Yonsei Medical Journal
Yihong Li, Dun Liu, Xinhua Zhang, Zhiming Li, Yuhua Ye, Qifa Liu, Jie Shen, Zhi Chen, Huajie Huang, Yunhao Liang, Xu Han, Jing Liu, Xiuli An, Narla Mohandas, Xiangmin Xu
Haplo-insufficiency of Erythroid Krüppel-like factor (EKLF/KLF1) has recently been shown to ameliorate the clinical severity of β-thalassemia by increased expression levels of fetal hemoglobin (HbF). The underlying mechanisms for role of EKLF in regulating HbF are of great interest but remain incompletely understood. In this study, we used a combination of in silico, in vitro, and in vivo approaches to identify microRNAs involved in EKLF regulation and to validate the role of miR-326 in HbF modification. We found that miR-326 directly suppresses EKLF expression by targeting its 3' untranslated region (3'UTR)...
March 27, 2018: Experimental Hematology
Zhonglin Zhu, Zhilong Yu, Jianfeng Wang, Lisheng Zhou, Jing Zhang, Bin Yao, Jin Dou, Zhengjun Qiu, Chen Huang
BACKGROUND/AIMS: Krüppel-like factor 4 (KLF4), a member of the KLF family of zinc finger transcription factors, has been identified as a tumor suppressor gene in a variety of tumors. However, the molecular mechanisms by which KLF4 inhibits epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic cancer remain unclear. METHODS: KLF4 expression in pancreatic cancer was analyzed using public datasets (Oncomine and The Cancer Genome Atlas). The expression of KLF4, caveolin-1 (Cav-1), E-cadherin, and vimentin, and their correlations with clinicopathological characteristics were evaluated by immunohistochemistry in pancreatic cancer tissues...
March 21, 2018: Cellular Physiology and Biochemistry
Sarah Smith-Moore, Stuart J D Neil, Cornel Fraefel, R Michael Linden, Mathieu Bollen, Helen M Rowe, Els Henckaerts
Adeno-associated virus (AAV) is a small human Dependovirus whose low immunogenicity and capacity for long-term persistence have led to its widespread use as vector for gene therapy. Despite great recent successes in AAV-based gene therapy, further improvements in vector technology may be hindered by an inadequate understanding of various aspects of basic AAV biology. AAV is unique in that its replication is largely dependent on a helper virus and cellular factors. In the absence of helper virus coinfection, wild-type AAV establishes latency through mechanisms that are not yet fully understood...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Emily V W Setton, Prashant P Sharma
The jointed appendages of arthropods have facilitated the spectacular diversity and success of this phylum. Key to the regulation of appendage outgrowth is the Krüppel-like factor (KLF)/specificity protein (Sp) family of zinc finger transcription factors. In the fruit fly, Drosophila melanogaster , the Sp6-9 homolog is activated by Wnt-1/wingless ( wg ) and establishes ventral appendage (leg) fate. Subsequently, Sp6-9 maintains expression of the axial patterning gene Distal-less ( Dll ), which promotes limb outgrowth...
March 26, 2018: Proceedings of the National Academy of Sciences of the United States of America
Emanuele Panatta, Anna Maria Lena, Mara Mancini, Michela Affinati, Artem Smirnov, Margherita Annicchiarico-Petruzzelli, Maria Cristina Piro, Elena Campione, Luca Bianchi, Cinzia Mazzanti, Gerry Melino, Eleonora Candi
Keratinocyte replicative senescence has an important role in time-related changes of epidermis. Previous studies demonstrated that miRNAs play key roles in inhibiting proliferation and in the acquisition of the keratinocyte senescent phenotype as well as in individual ageing. Kruppel-like factor 4 is a transcription factor with dual functions in keratinocytes, being a stemness factor and a pro-differentiation factor. Interestingly, in skin squamous cell carcinomas KLF4 expression is strongly down-regulated or absent...
March 23, 2018: Biochemical and Biophysical Research Communications
Miaoyun Wen, Jingkun Ye, Yongli Han, Linqiang Huang, Hui Yang, Wenqiang Jiang, Shenglong Chen, Wenhong Zhong, Hongke Zeng, Daniel Y Li
BACKGROUND: Hypertonic saline (HS) has been used clinically for treatment of cerebral edema for decades. Previously we have demonstrated that HS alleviates cerebral edema via regulating water/ion channel protein and attenuating neuroinflammation. However, whether HS treatment triggers microglia polarization and its regulatory mechanism during this process is unclear. METHODS AND RESULTS: The Sprague-Dawley (SD) rats that underwent right-sided middle cerebral artery occlusion (MCAO) were used for assessment of neuroinflammation and microglia functions...
March 26, 2018: Biochemical and Biophysical Research Communications
Michael J Mutolo, Shih-Hsing Leir, Sara L Fossum, James A Browne, Ann Harris
Mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene cause the inherited disorder cystic fibrosis (CF). Lung disease is the major cause of CF morbidity, though CFTR expression levels are substantially lower in the airway epithelium than in pancreatic duct and intestinal epithelia, which also show compromised function in CF. Recently developed small molecule therapeutics for CF are highly successful for one specific CFTR mutation and may have a positive impact on others. However, the low abundance of CFTR transcripts in the airway limits the opportunity for drugs to correct the defective substrate...
March 23, 2018: Biochemical Journal
Xiaoli Ding, Tianyu Zhong, Lixia Jiang, Junyun Huang, Yu Xia, Rong Hu
In recent years, microRNAs (miRNAs/miRs) have gained increasing interest in cancer research. Increasing evidences demonstrated that miRNAs are important for tumor early detection and prognosis. The present study aimed to explore the function of miR‑25 in non‑small‑cell lung cancer (NSCLC) and its underlying mechanisms. The expression levels of miR‑25 and Krüppel-like factor 4 (KLF4) were assessed in 31 pairs of tissue from patients with NSCLC. In addition, the biological roles of miR‑25 in NSCLC were analyzed via a cell wound healing assay, Transwell invasion and migration assays...
March 16, 2018: Molecular Medicine Reports
Tianlei Zhang, Wei Song, Zheng Li, Wenliang Qian, Ling Wei, Yan Yang, Weina Wang, Xuan Zhou, Meng Meng, Jian Peng, Qingyou Xia, Norbert Perrimon, Daojun Cheng
In insects, juvenile hormone (JH) and the steroid hormone ecdysone have opposing effects on regulation of the larval-pupal transition. Although increasing evidence suggests that JH represses ecdysone biosynthesis during larval development, the mechanism underlying this repression is not well understood. Here, we demonstrate that the expression of the Krüppel homolog 1 (Kr-h1), a gene encoding a transcription factor that mediates JH signaling, in ecdysone-producing organ prothoracic gland (PG) represses ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes in both Drosophila and Bombyx Application of a JH mimic on ex vivo cultured PGs from Drosophila and Bombyx larvae induces Kr-h1 expression and inhibits the transcription of steroidogenic enzymes...
March 22, 2018: Proceedings of the National Academy of Sciences of the United States of America
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