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https://www.readbyqxmd.com/read/28075452/a-novel-pathway-in-nsclc-cells-mir%C3%A2-191-targeting-nfia-is-induced-by-chronic-hypoxia-and-promotes-cell-proliferation-and-migration
#1
Jia Zhao, Cheng-Rui Qiao, Zheng Ding, Yin-Liang Sheng, Xiang-Nan Li, Yang Yang, Deng-Yan Zhu, Chun-Yang Zhang, Dong-Lei Liu, Kai Wu, Song Zhao
MicroRNAs (miRs) have emerged as being important in cancer biology. miR‑191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)‑1α and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR‑191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non‑small cell lung cancer (NSCLC) cells in patients in vivo...
January 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28063005/albendazole-inhibits-hif-1%C3%AE-dependent-glycolysis-and-vegf-expression-in-non-small-cell-lung-cancer-cells
#2
Fang Zhou, Jin Du, Jianjun Wang
Albendazole (ABZ) has an anti-tumor ability and inhibits HIF-1α activity. HIF-1α is associated with glycolysis and vascular endothelial cell growth factor (VEGF) expression, which plays an important role in cancer progression. These clues indicate that ABZ exerts an anti-cancer effect by regulating glycolysis and VEGF expression. The aim of this study is to clarify the effects of ABZ on non-small cell lung cancer (NSCLC) cells and explore the underlying molecular mechanisms. The expression levels of HIF-1α and VEGF were detected using western blot analysis, and the effect of ABZ on glycolysis was evaluated by measuring the relative activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) and detecting the production of lactate in A549 and H1299 cells...
January 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28062918/glycine-decarboxylase-and-hif-1%C3%AE-expression-are-negative-prognostic-factors-in-primary-resected-early-stage-non-small-cell-lung-cancer
#3
Sabina Berezowska, José A Galván, Rupert Langer, Lukas Bubendorf, Spasenija Savic, Mathias Gugger, Ralph A Schmid, Thomas M Marti
Glycine decarboxylase (GLDC) was recently described as a critical enzyme of tumor-initiating cells and, thus, a driver of tumorigenesis in lung non-small cell cancer (NSCC). It is important in metabolism under hypoxic conditions. Hypoxia-inducible factor 1-alpha (HIF-1α) is the unique subunit that determines HIF system activity, thereby regulating the adverse effects of hypoxia on cancer outcome. We examined the expression and prognostic significance of GLDC and HIF-1α in primary resected stage I/II NSCC...
January 7, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28045433/functions-and-epigenetic-regulation-of-wwox-in-bone-metastasis-from-breast-carcinoma-comparison-with-primary-tumors
#4
REVIEW
Paola Maroni, Emanuela Matteucci, Paola Bendinelli, Maria Alfonsina Desiderio
Epigenetic mechanisms influence molecular patterns important for the bone-metastatic process, and here we highlight the role of WW-domain containing oxidoreductase (Wwox). The tumor-suppressor Wwox lacks in almost all cancer types; the variable expression in osteosarcomas is related to lung-metastasis formation, and exogenous Wwox destabilizes HIF-1α (subunit of Hypoxia inducible Factor-1, HIF-1) affecting aerobic glycolysis. Our recent studies show critical functions of Wwox present in 1833-osteotropic clone, in the corresponding xenograft model, and in human bone metastasis from breast carcinoma...
January 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28042952/uncoupling-protein-2-downregulation-by-hypoxia-through-repression-of-peroxisome-proliferator-activated-receptor-%C3%AE-promotes-chemoresistance-of-non-small-cell-lung-cancer
#5
Mingxing Wang, Guoyin Li, Zhiwei Yang, Lei Wang, Lei Zhang, Ting Wang, Yimeng Zhang, Shengli Zhang, Yong Han, Lintao Jia
Hypoxic microenvironment is critically involved in the response of non-small cell lung cancer (NSCLC) to chemotherapy, the mechanisms of which remain largely unknown. Here, we found that NSCLC patients exhibited increased chemotherapeutic resistance when complicated by chronic obstructive pulmonary disease (COPD), a critical cause of chronic hypoxemia. The downregulation of uncoupling protein 2 (UCP2), which is attributed to hypoxia-inducible factor 1 (HIF-1)-mediated suppression of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), was involved in NSCLC chemoresistance, and predicted a poor survival rate of patients receiving routine chemotherapy...
December 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/28036300/evolutionary-selected-tibetan-variants-of-hif-pathway-and-risk-of-lung-cancer
#6
Lucie Lanikova, N Scott Reading, Hao Hu, Tsewang Tashi, Tatiana Burjanivova, Anna Shestakova, Bhola Siwakoti, Binay Kumar Thakur, Chin Bahadur Pun, Amir Sapkota, Sarah Abdelaziz, Bing-Jian Feng, Chad D Huff, Mia Hashibe, Josef T Prchal
Tibetans existed in high altitude for ~25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/PHD2 and EPAS1/HIF-2α, both crucial components of hypoxia sensing, are the two best-established loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2:p.[D4E /C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay; however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/HIF-2α have not yet been identified...
December 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031935/interaction-between-hypoxia-akt-and-hif-1-signaling-in-hnscc-and-nsclc-implications-for-future-treatment-strategies
#7
Hanneke Stegeman, Paul N Span, Wenny Jm Peeters, Marieke Mg Verheijen, Reidar Grénman, Tineke Wh Meijer, Johannes Ham Kaanders, Johan Bussink
BACKGROUND: Hypoxia is a negative prognostic factor and this study investigated the relationship between hypoxia, hypoxia inducible factor 1 (HIF-1) and AKT signaling in head and neck squamous cell carcinoma (HNSCC) and non-small-cell lung cancer (NSCLC). RESULTS/METHODOLOGY: pAKT was induced by hypoxia (0.5% O2) in a part of HNSCC (3/4) and squamous (2/3) and adenocarcinoma (1/3) NSCLS lines. AKT-inhibitor MK-2206 reduced hypoxic HIF-1 signaling in most HNSCC cell lines...
March 2016: Future Science OA
https://www.readbyqxmd.com/read/28028936/hypoxia-inducible-factor-1-promotes-chemoresistance-of-lung-cancer-by-inducing-carbonic-anhydrase-ix-expression
#8
Terumasa Sowa, Toshi Menju, Toyofumi F Chen-Yoshikawa, Koji Takahashi, Shigeto Nishikawa, Takao Nakanishi, Kei Shikuma, Hideki Motoyama, Kyoko Hijiya, Akihiro Aoyama, Toshihiko Sato, Makoto Sonobe, Hiroshi Harada, Hiroshi Date
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia-inducible factor 1 (HIF-1) and HIF-1-induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF-1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF-1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro...
December 28, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/28004751/daxx-inhibits-hypoxia-induced-lung-cancer-cell-metastasis-by-suppressing-the-hif-1%C3%AE-hdac1-slug-axis
#9
Ching-Wen Lin, Lu-Kai Wang, Shu-Ping Wang, Yi-Liang Chang, Yi-Ying Wu, Hsuan-Yu Chen, Tzu-Hung Hsiao, Wei-Yun Lai, Hsuan-Hsuan Lu, Ya-Hsuan Chang, Shuenn-Chen Yang, Ming-Wei Lin, Chi-Yuan Chen, Tse-Ming Hong, Pan-Chyr Yang
Hypoxia is a major driving force of cancer invasion and metastasis. Here we show that death domain-associated protein (Daxx) acts to negatively regulate hypoxia-induced cell dissemination and invasion by inhibiting the HIF-1α/HDAC1/Slug pathway. Daxx directly binds to the DNA-binding domain of Slug, impeding histone deacetylase 1 (HDAC1) recruitment and antagonizing Slug E-box binding. This, in turn, stimulates E-cadherin and occludin expression and suppresses Slug-mediated epithelial-mesenchymal transition (EMT) and cell invasiveness...
December 22, 2016: Nature Communications
https://www.readbyqxmd.com/read/28000380/quercetin-inhibits-sodium-nitrite-induced-inflammation-and-apoptosis-in-different-rats-organs-by-suppressing-bax-hif1-%C3%AE-tgf-%C3%AE-smad-2-and-akt-pathways
#10
Nouf Mohamed Al-Rasheed, Laila Mohamed Fadda, Hala A Attia, Hanaa Mahmoud Ali, Nawal Mohamed Al-Rasheed
The objective of this work is to study the protective effects of Quercetin against sodium nitrite-induced hypoxia on liver, lung, kidney and cardiac tissues, also to explore novel mechanism of this compound. Male albino rats were injected with sodium nitrite (75 mg/kg). Quercetin (200 mg kg(-1) ,- i.p.) was administrated 24 and 1 h respectively prior to sodium nitrite intoxication, hypoxia significantly decreased hemoglobin concentration, while increased expressions of HIF, Bax, Smad-2, TGF-β, and AKT...
December 21, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/27999195/molecular-and-functional-evaluation-of-a-novel-hif-inhibitor-benzopyranyl-1-2-3-triazole-compound
#11
Kyunghye Park, Hye Eun Lee, Sun Hee Lee, Doohyun Lee, Taeho Lee, You Mie Lee
Hypoxia occurs in a variety of pathological events, including the formation of solid tumors. Hypoxia-inducible factor (HIF)-1α is stabilized under hypoxic conditions and is a key molecule in tumor growth and angiogenesis. Seeking to develop novel cancer therapeutics, we investigated small molecules from our in-house chemical libraries to target HIF-1α. We employed a dual-luciferase assay that uses a luciferase (Luc) reporter vector harboring five copies of hypoxia-responsive element (HRE) in the promoter...
December 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994500/resveratrol-alleviate-hypoxic-pulmonary-hypertension-via-anti-inflammation-and-anti-oxidant-pathways-in-rats
#12
Dunquan Xu, Yan Li, Bo Zhang, Yanxia Wang, Yi Liu, Ying Luo, Wen Niu, Mingqing Dong, Manling Liu, Haiying Dong, Pengtao Zhao, Zhichao Li
Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development...
2016: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/27982675/differential-responsiveness-in-vegf-receptor-subtypes-to-hypoxic-stress-in-various-tissues-of-plateau-animals
#13
Hui-Chun Xie, Jin-Gang Li, Jian-Ping He
With hypoxic stress, hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are elevated and their responses are altered in skeletal muscles of plateau animals [China Qinghai-Tibetan plateau pikas (ochotona curzoniae)] as compared with control animals [normal lowland Sprague-Dawley (SD) rats]. The results indicate that HIF-1alpha and VEGF are engaged in physiological functions under hypoxic environment. The purpose of the current study was to examine the protein levels of VEGF receptor subtypes (VEGFRs: VEGFR-1, VEGFR-2 and VEGFR-3) in the end organs, namely skeletal muscle, heart and lung in response to hypoxic stress...
December 16, 2016: Physiological Research
https://www.readbyqxmd.com/read/27981753/association-between-genetic-polymorphisms-involved-in-the-hypoxia-inducible-factor-pathway-and-lung-cancer-risk-a-case-control-study-in-japan
#14
Yuzo Yamamoto, Chikako Kiyohara, Saiko Ogata-Suetsugu, Naoki Hamada, Yoichi Nakanishi
AIM: Hypoxia-inducible factor (HIF) contributes to the adaptation of tumor cells to hypoxic conditions, so genetic polymorphisms involved in this pathway may affect cellular response to hypoxia and be associated with cancer risk. Thus, we examined the association between the lung cancer risk and genetic polymorphisms involved in the HIF pathway. METHODS: This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of HIF1A rs11549467, HIF1A rs11549465, HIF1A rs2057482, HIF2A rs13419896 and vascular endothelial growth factor A (VEGFA) rs833061 on the risk of lung cancer using TaqMan real-time PCR assay...
December 16, 2016: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/27966538/nqo1-inhibits-proteasome-mediated-degradation-of-hif-1%C3%AE
#15
Eun-Taex Oh, Jung-Whan Kim, Joon Mee Kim, Soo Jung Kim, Jae-Seon Lee, Soon-Sun Hong, Justin Goodwin, Robin J Ruthenborg, Myung Gu Jung, Hae-June Lee, Chul-Ho Lee, Eun Sung Park, Chulhee Kim, Heon Joo Park
Overexpression of NQO1 is associated with poor prognosis in human cancers including breast, colon, cervix, lung and pancreas. Yet, the molecular mechanisms underlying the pro-tumorigenic capacities of NQO1 have not been fully elucidated. Here we show a previously undescribed function for NQO1 in stabilizing HIF-1α, a master transcription factor of oxygen homeostasis that has been implicated in the survival, proliferation and malignant progression of cancers. We demonstrate that NQO1 directly binds to the oxygen-dependent domain of HIF-1α and inhibits the proteasome-mediated degradation of HIF-1α by preventing PHDs from interacting with HIF-1α...
December 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27959445/delphinidin-inhibits-angiogenesis-through-the-suppression-of-hif-1%C3%AE-and-vegf-expression-in-a549-lung-cancer-cells
#16
Mun-Hyeon Kim, Yun-Jeong Jeong, Hyun-Ji Cho, Hyang-Sook Hoe, Kwan-Kyu Park, Yoon-Yub Park, Yung Hyun Choi, Cheorl-Ho Kim, Hyeun-Wook Chang, Young-Ja Park, Il-Kyung Chung, Young-Chae Chang
Delphinidin, a polyphenol that belongs to the group of anthocyanidins and is abundant in many pigmented fruits and vegetables, possesses important antioxidant, anti‑inflammatory, anti-mutagenic and anticancer properties. In the present study, we investigated the inhibitory effects of delphinidin on vascular endothelial growth factor (VEGF) expression, an important factor involved in angiogenesis and tumor progression, in A549 human lung cancer cells. Delphinidin inhibited CoCl2- and epidermal growth factor (EGF)-induced VEGF mRNA expression and VEGF protein production...
December 7, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27935843/siderophores-more-than-stealing-iron
#17
Judith Behnsen, Manuela Raffatellu
Siderophores are small molecular iron chelators that are produced by microbes and whose most notable function is to sequester iron from the host and provide this essential metal nutrient to microbes. Recent studies have proposed additional, noncanonical roles for siderophores, including the acquisition of noniron metals and modulation of host functions. Recently, Holden et al. (V. I. Holden, P. Breen, S. Houle, C. M. Dozois, and M. A. Bachman, mBio 7:e01397-16, 2016, http://dx.doi.org/10.1128/mBio.01397-16) showed that siderophores secreted by Klebsiella pneumoniae during lung infection induce stabilization of the transcription factor HIF-1α, increase the expression of proinflammatory cytokines in the lung, and promote dissemination of K...
November 15, 2016: MBio
https://www.readbyqxmd.com/read/27919930/mir-17-20-controls-prolyl-hydroxylase-2-phd2-hypoxia-inducible-factor-1-hif1-to-regulate-pulmonary-artery-smooth-muscle-cell-proliferation
#18
Tianji Chen, Qiyuan Zhou, Haiyang Tang, Melike Bozkanat, Jason X-J Yuan, J Usha Raj, Guofei Zhou
BACKGROUND: Previously we found that smooth muscle cell (SMC)-specific knockout of miR-17~92 attenuates hypoxia-induced pulmonary hypertension. However, the mechanism underlying miR-17~92-mediated pulmonary artery SMC (PASMC) proliferation remains unclear. We sought to investigate whether miR-17~92 regulates hypoxia-inducible factor (HIF) activity and PASMC proliferation via prolyl hydroxylases (PHDs). METHODS AND RESULTS: We show that hypoxic sm-17~92(-/-) mice have decreased hematocrit, red blood cell counts, and hemoglobin contents...
December 5, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#19
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27880046/docosahexaenoic-acid-mediated-inhibition-of-heat-shock-protein-90-p23-chaperone-complex-and-downstream-client-proteins-in-lung-and-breast-cancer
#20
Michael Mouradian, Irvin V Ma, Erika D Vicente, Keith D Kikawa, Ronald S Pardini
The molecular chaperone, heat shock protein 90 (Hsp90), is a critical regulator for the proper folding and stabilization of several client proteins, and is a major contributor to carcinogenesis. Specific Hsp90 inhibitors have been designed to target the ATP-binding site in order to prevent Hsp90 chaperone maturation. The current study investigated the effects of docosahexaenoic acid (DHA; C22:6 n-3) on Hsp90 function and downstream client protein expression. In vitro analyses of BT-474 human breast carcinoma and A549 human lung adenocarcinoma cell lines revealed dose-dependent decreases in intracellular ATP levels by DHA treatment, resulting in a significant reduction of Hsp90 and p23 association in both cell lines...
January 2017: Nutrition and Cancer
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