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https://www.readbyqxmd.com/read/28543190/effects-of-shrna-mediated-silencing-of-pkm2-gene-on-aerobic-glycolysis-cell-migration-cell-invasion-and-apoptosis-in-colorectal-cancer-cells
#1
Xiao-Ling Yan, Xue-Bin Zhang, Ran Ao, Lin Guan
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28522551/inhibition-of-mir-143-during-ischemia-cerebral-injury-protects-neurons-through-recovery-of-the-hexokinase-2-mediated-glucose%C3%A2-uptake
#2
Xianzhu Zeng, Na Liu, Jing Zhang, Lei Wang, Zhecheng Zhang, Ju Zhu, Qian Li, Yuwen Wang
Ischemic stroke, a major cause of death, is caused by occlusion of a blood vessel, resulting in a significant reduction in regional cerebral blood flow. MicroRNAs (miRNAs) are a family of short noncoding RNAs (18 to 22 nucleotides) and bind the 3' un-translated region (UTR) of their target genes to post-transcriptionally suppress gene expression. In this study, we report miR-143 is downregulated in rat neurons but high expressed in astrocytes cells. In vivo middle cerebral artery occlusion (MCAO) and ex vivo oxygen-glucose deprivation (OGD) results showed miR-143 was significantly induced by ischemia injury...
May 18, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28515149/pyruvate-kinase-inhibits-proliferation-during-postnatal-cerebellar-neurogenesis-and-suppresses-medulloblastoma-formation
#3
Katherine Tech, Andrey P Tikunov, Hamza Farooq, A Sorana Morrissy, Jessica Meidinger, Taylor Fish, Sarah C Green, Hedi Liu, Yisu Li, Andrew J Mungall, Richard A Moore, Yussanne Ma, Steven Jm Jones, Marco A Marra, Matthew G Vander Heiden, Michael D Taylor, Jeffrey MacDonald, Timothy R Gershon
Aerobic glycolysis supports proliferation through unresolved mechanisms. We have previously shown that aerobic glycolysis is required for the regulated proliferation of cerebellar granule neuron progenitors (CGNPs), and for the growth of CGNP-derived medulloblastoma. Blocking the initiation of glycolysis via deletion of Hexokinase-2 (Hk2) disrupts CGNP proliferation and restricts medulloblastoma growth. Here, we assessed whether disrupting Pyruvate kinase-M (Pkm), an enzyme that acts in the terminal steps of glycolysis, would alter CGNP metabolism, proliferation and tumorigenesis...
May 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28511909/discovery-and-structure-guided-fragment-linking-of-4-2-3-dichlorobenzoyl-1-methyl-pyrrole-2-carboxamide-as-a-pyruvate-kinase-m2-activator
#4
Yumi Matsui, Isao Yasumatsu, Takashi Asahi, Takahiro Kitamura, Kazuo Kanai, Osamu Ubukata, Hitoshi Hayasaka, Sachiko Takaishi, Hiroyuki Hanzawa, Shinichi Katakura
Tumor cells switch glucose metabolism to aerobic glycolysis by expressing the pyruvate kinase M2 isoform (PKM2) in a low active form, providing glycolytic intermediates as building blocks for biosynthetic processes, and thereby supporting cell proliferation. Activation of PKM2 should invert aerobic glycolysis to an oxidative metabolism and prevent cancer growth. Thus, PKM2 has gained attention as a promising cancer therapy target. To obtain novel PKM2 activators, we conducted a high-throughput screening (HTS)...
May 5, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28498807/knockdown-of-pkm2-and-gls1-expression-can-significantly-reverse-oxaliplatin-resistance-in-colorectal-cancer-cells
#5
Wei-Qun Lu, Ying-Ying Hu, Xiao-Ping Lin, Wei Fan
Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28495754/phd3-is-a-transcriptional-coactivator-of-hif-1%C3%AE-in-nucleus-pulposus-cells-independent-of-the-pkm2-jmjd5-axis
#6
Zachary R Schoepflin, Elizabeth S Silagi, Irving M Shapiro, Makarand V Risbud
The role of prolyl hydroxylase (PHD)-3 as a hypoxia inducible factor (HIF)-1α cofactor is controversial and remains unknown in skeletal tissues. We investigated whether PHD3 controls HIF-1 transcriptional activity in nucleus pulposus (NP) cells through the pyruvate kinase muscle (PKM)-2-Jumonji domain--containing protein (JMJD5) axis. PHD3(-/-) mice (12.5 mo old) showed increased incidence of intervertebral disc degeneration with a concomitant decrease in expression of the HIF-1α targets VEGF-A, glucose transporter-1, and lactate dehydrogenase A...
May 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28490692/-identification-of-the-interacting-proteins-with-s100a8-or-s100a9-by-affinity-purification-and-mass-spectrometry
#7
Jing Wang, Xuemei Zhang, Zheng Li, Xiayu Li, Jian Ma, Shourong Shen
To identify the interacting proteins with S100A8 or S100A9 in HEK293 cell line by flag-tag affinity purification and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS).
 Methods: The p3×Flag-CMV-S100A8 and p3×Flag-CMV-S100A9 expression vectors were constructed by inserting S100A8 or S100A9 coding sequence. The recombinant plasmids were then transfected into HEK293 cells. Affinity purification and LC-MS/MS were applied to identify the proteins interacting with S100A8 or S100A9. Bioinformatics analysis was used to seek the gene ontology of the interacting proteins...
April 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28489603/18f-fluorodeoxyglucose-uptake-predicts-pkm2-expression-in-lung-adenocarcinoma
#8
Ping Huang, Xiang Zhao, Weiyuan Xiao, Yuqi Dong, Guangyu Hu
Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2) plays a key role in glycolysis. We therefore investigated whether PKM2 expression affects 18F-FDG uptake in a retrospective analysis of 76 patients who underwent 18F-FDG PET/computed tomography (CT) scans for staging before surgical resection. We found that PKM2 expression was higher in tumors than peritumoral tissue (p < 0.05). Patients with high PKM2 expression had reduced overall (p < 0...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454440/ffj-3-inhibits-pkm2-protein-expression-via-the-pi3k-akt-signaling-pathway-and-activates-the-mitochondrial-apoptosis-signaling-pathway-in-human-cancer-cells
#9
Dengyun Li, Xiaoli Wei, Mingming Ma, Huina Jia, Yu Zhang, Wenyi Kang, Tianxiao Wang, Xiaoyan Shi
Pyruvate kinase isoenzyme M2 (PKM2) has previously been identified as a tumor biomarker and potential therapeutic target for the treatment of cancer. In the present study, FFJ-3, a structurally modified version of mollugin, an extract of the Traditional Chinese herbal medicine Rubia tinctorum (madder) was used in order to determine the anticancer activity of the compound and investigate the potential mechanisms underlying this effect in human cancer cells. The results of the present study revealed that FFJ-3 inhibited the survival of HepG2 human hepatoma cells, MCF-7 human breast cancer cells and A549 human lung adenocarcinoma cells using the MTT assay...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28446743/mammalian-target-of-rapamycin-mtor-regulates-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-via-decreased-pyruvate-kinase-m2-pkm2-expression-in-cervical-cancer-cells
#10
Ke-Yan Cheng, Min Hao
BACKGROUND Epithelial-mesenchymal transition (EMT) plays an important role in cancer tumorigenesis. Transforming growth factor β1 (TGF-β1) can induced EMT, which could increase tumor migration and invasion. Moreover, recent studies have been proven that mammalian target of rapamycin (mTOR) is a critical regulator of EMT. We investigated the mechanisms of mTOR in transforming growth factor β1 (TGF-β1)-induced EMT in cervical cancer cells. MATERIAL AND METHODS HeLa and SiHa cells were treated with 10 ng/ml TGF-β1 to induce EMT...
April 27, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28436957/pyruvate-kinase-m2-activation-may-protect-against-the-progression-of-diabetic-glomerular-pathology-and-mitochondrial-dysfunction
#11
Weier Qi, Hillary A Keenan, Qian Li, Atsushi Ishikado, Aimo Kannt, Thorsten Sadowski, Mark A Yorek, I-Hsien Wu, Samuel Lockhart, Lawrence J Coppey, Anja Pfenninger, Chong Wee Liew, Guifen Qiang, Alison M Burkart, Stephanie Hastings, David Pober, Christopher Cahill, Monika A Niewczas, William J Israelsen, Liane Tinsley, Isaac E Stillman, Peter S Amenta, Edward P Feener, Matthew G Vander Heiden, Robert C Stanton, George L King
Diabetic nephropathy (DN) is a major cause of end-stage renal disease, and therapeutic options for preventing its progression are limited. To identify novel therapeutic strategies, we studied protective factors for DN using proteomics on glomeruli from individuals with extreme duration of diabetes (ł50 years) without DN and those with histologic signs of DN. Enzymes in the glycolytic, sorbitol, methylglyoxal and mitochondrial pathways were elevated in individuals without DN. In particular, pyruvate kinase M2 (PKM2) expression and activity were upregulated...
April 24, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28426732/regulation-of-sesame-mediated-h3t11-phosphorylation-by-glycolytic-enzymes-and-metabolites
#12
Qi Yu, Chong Tong, Mingdan Luo, Xiangyan Xue, Qianyun Mei, Lixin Ma, Xiaolan Yu, Wuxiang Mao, Lingbao Kong, Xilan Yu, Shanshan Li
Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear...
2017: PloS One
https://www.readbyqxmd.com/read/28423551/metabolic-reprogramming-of-the-premalignant-colonic-mucosa-is-an-early-event-in-carcinogenesis
#13
Mart Dela Cruz, Sarah Ledbetter, Sanjib Chowdhury, Ashish K Tiwari, Navneet Momi, Ramesh K Wali, Charles Bliss, Christopher Huang, David Lichtenstein, Swati Bhattacharya, Anisha Varma-Wilson, Vadim Backman, Hemant K Roy
BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field. METHODS: Rectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28422979/correlation-of-egfr-or-kras-mutation-status-with-18f-fdg-uptake-on-pet-ct-scan-in-lung-adenocarcinoma
#14
Kazuya Takamochi, Kaoru Mogushi, Hideya Kawaji, Kota Imashimizu, Mariko Fukui, Shiaki Oh, Masayoshi Itoh, Yoshihide Hayashizaki, Weijey Ko, Masao Akeboshi, Kenji Suzuki
BACKGROUND: 18F-fluoro-2-deoxy-glucose (18F-FDG) positron emission tomography (PET) is a functional imaging modality based on glucose metabolism. The correlation between EGFR or KRAS mutation status and the standardized uptake value (SUV) of 18F-FDG PET scanning has not been fully elucidated. METHODS: Correlations between EGFR or KRAS mutation status and clinicopathological factors including SUVmax were statistically analyzed in 734 surgically resected lung adenocarcinoma patients...
2017: PloS One
https://www.readbyqxmd.com/read/28418088/rack1-forms-a-complex-with-fgfr1-and-pkm2-and-stimulates-the-growth-and-migration-of-squamous-lung-cancer-cells
#15
Chengzhi Zhou, Tao Chen, Zhanhong Xie, Yinyin Qin, Yangming Ou, Jiexia Zhang, Shiyue Li, Rongchang Chen, Nanshan Zhong
Phosphorylation of Pyruvate Kinase M2 (PKM2) on Tyr105 by fibroblast growth factor receptor 1 (FGFR1) has been shown to promote its nuclear localization as well as cell growth in lung cancer. Better understanding the regulation of this process would benefit the clinical treatment for lung cancer. Here, it has been found that the adaptor protein receptor for activated PKC kinase (RACK1) formed a complex with FGFR1 and PKM2, and activated the FGFR1/PKM2 signaling. Knocking down the expression of RACK1 impaired the phosphorylation on Tyr105 of PKM2 and inhibited the growth and migration of lung cancer cells, while over-expression of RACK1 in lung cancer cells led to the resistance to Erdafitinib...
April 18, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28415668/mir-let-7a-inhibits-cell-proliferation-migration-and-invasion-by-down-regulating-pkm2-in-cervical-cancer
#16
Man Guo, Xinying Zhao, Xiaolei Yuan, Jing Jiang, Peiling Li
In recent decades, miRNA has been reported as a crucial modulator in some biology progressions. This work aims to assess the expression and role of miR-let-7a and pyruvate kinase muscle isozyme M2 (PKM2) in CC tissues and cell lines. Here, we identified that miR-let-7a expression was decreased in CC tissues, and SiHa and HeLa cells (all P < 0.001), however, PKM2 expression was increased in these samples. Statistically, miR-let-7a was inversely associated with PKM2 mRNA or protein (p = 0.013, p = 0.015, respectively)...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414323/pyrimidine-tract-binding-protein-1-mediates-pyruvate-kinase-m2-dependent-phosphorylation-of-signal-transducer-and-activator-of-transcription-3-and-oncogenesis-in-anaplastic-large-cell-lymphoma
#17
Steven R Hwang, Carlos Murga-Zamalloa, Noah Brown, Johnvesly Basappa, Scott Rp McDonnell, Veronica Mendoza-Reinoso, Venkatesha Basrur, Ryan Wilcox, Kojo Elenitoba-Johnson, Megan S Lim
PKM2 (pyruvate kinase M2), a critical regulator of glycolysis, is phosphorylated by numerous growth factor receptors and oncogenic tyrosine kinases including NPM-ALK which is expressed in a subset of aggressive T-cell non-Hodgkin lymphomas known as anaplastic large cell lymphoma, ALK-positive. Our previous work demonstrated that phosphorylation of Y105-PKM2 by NPM-ALK regulates a major metabolic shift to promote lymphomagenesis. In addition to its role in metabolism, recent studies have shown that PKM2 promotes oncogenesis by phosphorylating nuclear STAT3 (signal transducer and activator of transcription 3) and regulating transcription of genes involved in cell survival and proliferation...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28398453/multi-step-encapsulation-of-chemotherapy-and-gene-silencing-agents-in-functionalized-mesoporous-silica-nanoparticles
#18
Jianliang Shen, Haoran Liu, Chaofeng Mu, Joy Wolfram, Wei Zhang, Han-Cheon Kim, Guixian Zhu, Zhongbo Hu, Liang-Nian Ji, Xuewu Liu, Mauro Ferrari, Zong-Wan Mao, Haifa Shen
Drug to carrier ratio is an important consideration in designing drug platforms, since a low loading capacity necessitates the use of high doses of carriers, which can result in side effects. Here, we have engineered a platform to co-deliver small molecule drugs and small interfering RNA (siRNA). This platform consists of cyclodextrin-grafted polyethylenimine (CP) functionalized mesoporous silica nanoparticles (MSNP). A unique multi-step encapsulation procedure was used to obtain a high loading capacity for doxorubicin (DOX) and siRNA oligos specific for the PKM2 gene that encodes pyruvate kinase M2, an enzyme catalyzing the final rate-limiting step in glycolysis...
April 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28394882/mir-4417-targets-tripartite-motif-containing-35-trim35-and-regulates-pyruvate-kinase-muscle-2-pkm2-phosphorylation-to-promote-proliferation-and-suppress-apoptosis-in-hepatocellular-carcinoma-cells
#19
Lijie Song, Weijie Zhang, Zhiwei Chang, Yanfeng Pan, Hong Zong, Qingxia Fan, Liuxing Wang
BACKGROUND MicroRNAs (miRNAs) are a class of small non-coding RNAs that are strongly involved in various types of carcinogenesis, including hepatocellular carcinoma (HCC). This study aimed to clarify whether miR-4417 promotes HCC growth by targeting TRIM35 and regulating PKM2 phosphorylation. MATERIAL AND METHODS Online software, including TargetScan and miRanda, was used to predict the potential target of miR-4417. Real-Time PCR (qRT-PCR) and Western blot assays were performed to detect the expression levels of mRNA and protein, respectively...
April 10, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28393220/metformin-increases-sensitivity-of-osteosarcoma-stem-cells-to-cisplatin-by-inhibiting-expression-of-pkm2
#20
Depeng Shang, Ju Wu, Lianyi Guo, Yanju Xu, Lezi Liu, Jianmin Lu
Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells...
May 2017: International Journal of Oncology
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