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Jing Wen, Ruitu Lv, Honghui Ma, Hongjie Shen, Chenxi He, Jiahua Wang, Fangfang Jiao, Hang Liu, Pengyuan Yang, Li Tan, Fei Lan, Yujiang Geno Shi, Chuan He, Yang Shi, Jianbo Diao
N6 -methyladenosine (m6 A) is an abundant modification in eukaryotic mRNA, regulating mRNA dynamics by influencing mRNA stability, splicing, export, and translation. However, the precise m6 A regulating machinery still remains incompletely understood. Here we demonstrate that ZC3H13, a zinc-finger protein, plays an important role in modulating RNA m6 A methylation in the nucleus. We show that knockdown of Zc3h13 in mouse embryonic stem cell significantly decreases global m6 A level on mRNA. Upon Zc3h13 knockdown, a great majority of WTAP, Virilizer, and Hakai translocate to the cytoplasm, suggesting that Zc3h13 is required for nuclear localization of the Zc3h13-WTAP-Virilizer-Hakai complex, which is important for RNA m6 A methylation...
March 15, 2018: Molecular Cell
Dong-Keon Lee, Ji-Hee Kim, Joohwan Kim, Seunghwan Choi, MinSik Park, Wonjin Park, Suji Kim, Kyu-Sun Lee, Taesam Kim, Jiwon Jung, Yoon Kyung Choi, Kwon-Soo Ha, Moo-Ho Won, Timothy R Billiar, Young-Guen Kwon, Young-Myeong Kim
Regulated in development and DNA damage responses (REDD)-1, an inhibitor of mammalian target of rapamycin (mTOR), is induced by various cell stressors, including LPS, a major player in the pathogenesis of endotoxemic shock. However, the pathologic role of REDD-1 in endotoxemia is largely unknown. We found that LPS increased REDD-1 expression, nuclear transcription factor-κB (NF-κB) activation, and inflammation and that these responses were suppressed by REDD-1 knockdown and in REDD-1+/- macrophages. REDD-1 overexpression stimulated NF-κB-dependent inflammation without additional LPS stimulation...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Eva Jover, Ana Silvente, Francisco Marín, José Martínez-González, Mar Orriols, Carlos M Martinez, Carmen María Puche, Mariano Valdés, Cristina Rodriguez, Diana Hernández-Romero
Vascular smooth muscle cells (VSMCs) transdifferentiate into osteoblast-like cells during vascular calcification, inducing active remodeling and calcification of the extracellular matrix (ECM). Intracellular and extracellular enzymes, such as lysyl hydroxylase 1 (PLOD1) and lysyl oxidase (LOX), contribute to ECM maturation and stabilization. We assessed the contribution of these enzymes to hyperphosphatemia (HPM)-induced calcification. Human and murine VSMCs were differentiated into functional osteoblast-like cells by HPM conditioning...
March 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Sribalasubashini Muralimanoharan, Youn-Tae Kwak, Carole R Mendelson
Dysregulation of human trophoblast invasion and differentiation with placental hypoxia can result in preeclampsia, a hypertensive disorder of pregnancy. Herein, we characterized the role and regulation of miR-1246, which is markedly induced during human syncytiotrophoblast differentiation. miR-1246 is known to target GSK3β and AXIN2, inhibitors of WNT/β-catenin signaling, which is crucial for placental development, and is predicted to target JARID2, which promotes silencing of developmentally regulated genes...
March 13, 2018: Endocrinology
Yanlan Li, Xiaodan Liu, Pengchao Gong, Xin Tian
Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection...
March 13, 2018: Carcinogenesis
Jilong Zhou, Chengyu Li, Wang Yao, Alsiddig M A, Lijun Huo, Honglin Liu, Yi-Liang Miao
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we showed that autophagy was essential for the glycolysis switch and energy homeostasis in mouse granulosa cells (MGCs) under hypoxic condition. Our data indicated that hypoxia inducible factor-1α (HIF-1α) could be largely increased in developing follicles and this remarkable upregulation of HIF-1α triggered cell autophagy and glucose uptake. We found that blocking autophagy by Atg7 knockdown and 3-methyladenine (3-MA) treatment affected the glucose metabolism, with increased glycolytic enzyme activity and decreased ATP production...
March 13, 2018: Biology of Reproduction
Hua Zhou, Abdul Mondal, Aleksandra Dakic, Lama Alhawas, Xuefeng Liu, Zhixu He
The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot...
2018: BioMed Research International
Christine Ludwin Wanjala, Eliningaya J Kweka
Background: Malaria vector control efforts have taken malaria related cases down to appreciable number per annum after large scale of intervention tools. Insecticides-based tools remain the major control option for malaria vectors in Kenya and, therefore, the potential of such programs to be compromised by the reported insecticide resistance is of major concern. The objective of this study was to evaluate the status of insecticide resistance in malaria vectors in different agro ecosystems from western Kenya...
2018: Frontiers in Public Health
Yunwu Wang, Yu Xu, Wei Yan, Ping Han, Jingmei Liu, Jin Gong, Dongxiao Li, Xiangming Ding, Han Wang, Zhuoying Lin, Dean Tian, Jiazhi Liao
Alternative polyadenylation (APA), a post-transcriptional modification, has been implicated in many diseases, but especially in tumor proliferation. CFIm25, the 25 kDa subunit of human cleavage factor Im (CFIm), is a key factor in APA. We show that CFIm25 expression is reduced in human hepatocellular carcinoma (HCC), and its expression correlates with metastasis. Kaplan-Meier analysis indicated that CFIm25 is related to overall survival in HCC. Moreover, CFIm25 expression is negatively related to the metastatic potential of HCC cell lines...
February 20, 2018: Oncotarget
Muhammad Mosaraf Hossain, David Barua, Vahid Arabkari, Nahidul Islam, Ananya Gupta, Sanjeev Gupta
Nuclear receptor coactivators (NCOAs) function as coactivators for nuclear receptors as well as several other transcription factors and potentiate their transcriptional activity. NCOAs play an important role in biology of hormone-dependent and -independent cancers. MCB-613 is a recently described, small molecule stimulator of NCOAs and anti-neoplastic compound that leads to the death of tumour cells due to increased cellular stress. In the present study we investigated the molecular mechanism of MCB-613-induced cell death...
February 20, 2018: Oncotarget
Koji Yamamoto, Makiko Kawaguchi, Takeshi Shimomura, Aya Izumi, Kazuomi Konari, Arata Honda, Chen-Yong Lin, Michael D Johnson, Yoshihiro Yamashita, Tsuyoshi Fukushima, Hiroaki Kataoka
Hepatocyte growth factor activator inhibitor (HAI)-1/ SPINT1 and HAI-2/ SPINT2 are membrane-anchored protease inhibitors having homologous Kunitz-type inhibitor domains. They regulate membrane-anchored serine proteases, such as matriptase and prostasin. Whereas HAI-1 suppresses the neoplastic progression of keratinocytes to invasive squamous cell carcinoma (SCC) through matriptase inhibition, the role of HAI-2 in keratinocytes is poorly understood. In vitro homozygous knockout of the SPINT2 gene suppressed the proliferation of two oral SCC (OSCC) lines (SAS and HSC3) but not the growth of a non-tumorigenic keratinocyte line (HaCaT)...
February 20, 2018: Oncotarget
Qiujun Liu, Xianyao Zhou, Chuan Li, Xuemei Zhang, Chang Long Li
There is limited knowledge regarding the influence of autophagy on the anticancer effect of dihydroartemisinin (DHA). The present study aimed to investigate this influence within human breast cancer cells. Changes in cell viability, cell cycle distribution, apoptosis and associated genes were analyzed in MDA-MB-231 cells subjected to DHA following alteration in autophagy levels; the autophagy level was decreased following autophagy-related 7 (Atg7) knockdown or increased using rapamycin. The data indicated that rapamycin had the ability to notably enhance the anticancer effect of DHA on MDA-MB-231 cells...
April 2018: Oncology Letters
Ron Stauder, Ralf Welsch, Maurizio Camagna, Wouter Kohlen, Gerd U Balcke, Alain Tissier, Michael H Walter
Strigolactones (SLs) are apocarotenoid phytohormones synthesized from carotenoid precursors. They are produced most abundantly in roots for exudation into the rhizosphere to cope with mineral nutrient starvation through support of root symbionts. Abscisic acid (ABA) is another apocarotenoid phytohormone synthesized in roots, which is involved in responses to abiotic stress. Typically low carotenoid levels in roots raise the issue of precursor supply for the biosynthesis of these two apocarotenoids in this organ...
2018: Frontiers in Plant Science
Seow Theng Ong, Madhavi Latha Somaraju Chalasani, M H U Turabe Fazil, Praseetha Prasannan, Atish Kizhakeyil, Graham D Wright, Dermot Kelleher, Navin Kumar Verma
Centrosome- and Golgi-localized protein kinase N-associated protein (CG-NAP), also known as AKAP450, is a cytosolic scaffolding protein involved in the targeted positioning of multiple signaling molecules, which are critical for cellular functioning. Here, we show that CG-NAP is predominantly expressed in human primary T-lymphocytes, localizes in close proximity (<0.2 μm) with centrosomal and Golgi structures and serves as a docking platform for Protein Kinase A (PKA). GapmeR-mediated knockdown of CG-NAP inhibits LFA-1-induced T-cell migration and impairs T-cell chemotaxis toward the chemokine SDF-1α...
2018: Frontiers in Immunology
S Wang, Z Zou, X Luo, Y Mi, H Chang, D Xing
Liver receptor homolog-1 (LRH1) has been shown to promote tumor proliferation and development. However, the functions of LRH1 in mediating cancer cells chemoresistance are still not clear. Here, we found LRH1 levels were significantly elevated in primary breast cancer tissues in patients who developed early recurrence. Similarly, adriamycin (ADR)-resistant breast cancer cell lines also exerted high LRH1 expression. Indeed, overexpression of LRH1 attenuated cytotoxicity of chemotherapeutic drugs ADR and cisplatin (DDP) in breast cancer cells in vitro and in nude mice tumor model...
March 16, 2018: Oncogene
Shun-Fan Wu, Bin Zeng, Chen Zheng, Xi-Chao Mu, Yong Zhang, Jun Hu, Shuai Zhang, Cong-Fen Gao, Jin-Liang Shen
The brown planthopper, Nilaparvata lugens, is an economically important pest on rice in Asia. Chemical control is still the most efficient primary way for rice planthopper control. However, due to the intensive use of insecticides to control this pest over many years, resistance to most of the classes of chemical insecticides has been reported. In this article, we report on the status of eight insecticides resistance in Nilaparvata lugens (Stål) collected from China over the period 2012-2016. All of the field populations collected in 2016 had developed extremely high resistance to imidacloprid, thiamethoxam, and buprofezin...
March 15, 2018: Scientific Reports
Pingping Fang, Jill A Madden, Lisa Neums, K Ryan Moulder, M Laird Forrest, Jeremy Chien
FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in poly (ADP-ribose) polymerase (PARP) inhibitor response has not yet been studied. The present study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. Based on ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair...
March 15, 2018: Molecular Cancer Research: MCR
Dinghui Yu, Ying Tan, Molee Chakraborty, Seth Tomchik, Ronald L Davis
The evolutionarily conserved Elongator Complex associates with RNA polymerase II for transcriptional elongation. Elp3 is the catalytic subunit, contains histone acetyltransferase activity, and is associated with neurodegeneration in humans. Elp1 is a scaffolding subunit and when mutated causes familial dysautonomia. Here, we show that elp3 and elp1 are required for aversive long-term olfactory memory in Drosophila RNAi knockdown of elp3 in adult mushroom bodies impairs long-term memory (LTM) without affecting earlier forms of memory...
April 2018: Learning & Memory
Shu Meng, Qilin Gu, Xiaojie Yang, Jie Lv, Iris Owusu, Gianfranco Matrone, Kaifu Chen, John P Cooke, Longhou Fang
Background -Angiogenesis is integral for embryogenesis, and targeting angiogenesis improves the outcome of many pathological conditions in patients. TBX20 is a crucial transcription factor for embryonic development, and its deficiency is associated with congenital heart disease. However, the role of TBX20 in angiogenesis has not been described. Methods -Loss- and gain-of-function approaches were used to explore the role of TBX20 in angiogenesis both in vitro and in vivo Angiogenesis gene array was used to identify key downstream targets of TBX20...
March 15, 2018: Circulation
Natalia Papadopoulos, Johan Lennartsson, Carl-Henrik Heldin
Translocation of full-length or fragments of receptors to the nucleus has been reported for several tyrosine kinase receptors. In this paper, we show that a fraction of full-length cell surface platelet-derived growth factor (PDGF) receptor β (PDGFRβ) accumulates in the nucleus at the chromatin and the nuclear matrix after ligand stimulation. Nuclear translocation of PDGFRβ was dependent on PDGF-BB-induced receptor dimerization, clathrin-mediated endocytosis, β-importin, and intact Golgi, occurring in both normal and cancer cells...
March 15, 2018: Journal of Cell Biology
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