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Stephen Safe, James L Abbruzzese, Maen Abdelrahim, Erik Hedrick
Specificity protein (Sp) transcription factors (TFs) such as Sp1 are critical for early development but their expression decreases with age and there is evidence that transformation of normal cells to cancer cells is associated with upregulation of Sp1, Sp3 and Sp4 which are highly expressed in cancer cells and tumors. Sp1 is a negative prognostic factor for pancreatic, colon, glioma, gastric, breast, prostate, and lung cancer patients. Functional studies also demonstrate that Sp TFs regulate genes responsible for cancer cell growth, survival, migration/invasion, inflammation and drug resistance, and Sp1, Sp3 and Sp4 are also non-oncogene addiction (NOA) genes and important drug targets...
March 15, 2018: Cancer Prevention Research
Aleksandra Augusciak-Duma, Joanna Witecka, Aleksander L Sieron, Magdalena Janeczko, Jacek J Pietrzyk, Karolina Ochman, Anna Galicka, Maria K Borszewska-Kornacka, Jacek Pilch, Elzbieta Jakubowska-Pietkiewicz
Although over 85% of osteogenesis imperfecta (OI) cases are associated with mutations in the procollagen type I genes (COL1A1 or COL1A2), no hot spots for the mutations were associated with particular clinical phenotypes. Eight patients that were studied here, diagnosed with OI by clinical standards, are from the Polish population with no ethnic background indicated. Previously unpublished mutations were found in six out of those eight patients. Genotypes for polymorphisms (Sp1 - rs1800012 and PvuII - rs412777), linked to bone formation and metabolism were determined...
March 15, 2018: Acta Biochimica Polonica
Matharage Gayani Dilshara, Rajapaksha Gedara Prasad Tharanga Jayasooriya, Ilandarage Menu Neelaka Molagoda, Jin-Woo Jeong, Seungheon Lee, Sang Rul Park, Gi-Young Kim, Yung Hyun Choi
In this study, we addressed how silibinin enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in various cancer cells. Combined treatment with silibinin and TRAIL (silibinin/TRAIL) induced apoptosis accompanied by the activation of caspase-3, caspase-8, caspase-9, and Bax, and cytosolic accumulation of cytochrome c. Anti-apoptotic proteins such as Bcl-2, IAP-1, and IAP-2 were inhibited as well. Silibinin also triggered TRAIL-induced apoptosis in A549 cells through upregulation of death receptor 5 (DR5)...
February 13, 2018: Oncotarget
Xin Shi, Shengcai Wei, Kevin J Simms, Devan N Cumpston, Thomas J Ewing, Ping Zhang
Activation and reprogramming of hematopoietic stem/progenitor cells play a critical role in the granulopoietic response to bacterial infection. Our current study determined the significance of Sonic hedgehog (SHH) signaling in the regulation of hematopoietic precursor cell activity during the host defense response to systemic bacterial infection. Bacteremia was induced in male Balb/c mice via intravenous injection (i.v.) of Escherichia coli (5 × 107 CFUs/mouse). Control mice received i.v. saline. SHH protein level in bone marrow cell (BMC) lysates was markedly increased at both 24 and 48 h of bacteremia...
2018: Frontiers in Immunology
Natascia Guida, Valeria Valsecchi, Giusy Laudati, Angelo Serani, Luigi Mascolo, Pasquale Molinaro, Paolo Montuori, Gianfranco Di Renzo, Lorella M T Canzoniero, Luigi Formisano
Methylmercury (MeHg) causes neuronal death through different pathways. Particularly, we found that in cortical neurons it increased the expression of Repressor Element-1 Silencing Transcription Factor (REST), Histone Deacetylase (HDAC)4, Specificity Protein (Sp)1, Sp4 and reduced the levels of Brain-Derived Neurotrophic Factor (BDNF). Herein, in rat cortical neurons we investigated whether microRNA (miR)206 can modulate MeHg-induced cell death by regulating REST/HDAC4/Sp1/Sp4/BDNF axis. MeHg (1µM) reduced miR206 expression after both 12 and 24 hours and miR206 transfection prevented MeHg-induced neuronal death...
March 7, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Lihua Zhu, Jia Li, Wu Dayang, Li Bing
PURPOSE: To investigate the protective effect of beta-casomorphin-7 (β-CM-7) in oxidative stressed human lens epithelial cells (HLECs) and to explore the possible mechanism for oxidative stress in human lens epithelial cells induced by high glucose. METHODS: We used HLECs to determine the effect of different concentrations of β-CM-7 on cell viability by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolimol/L bromide (MTT) assay. We used flow cytometry to determine the content of reactive oxygen species (ROS) induced by oxidative stress and a bioassay kit to determine the oxidant malondialdehyde (MDA) and antioxidant enzyme superoxide dismutase (SOD) levels...
March 8, 2018: Cutaneous and Ocular Toxicology
A Tuğşen Aydemir, Meltem Alper, Feray Köçkar
ADAMTS3 is a member of procollagen N-proteinase subfamily of ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) gene family. It has an important function in the procollagen maturation process. The removal of N-peptidases is required for the accurate processing of fibrillar collagens. Otherwise, several disorders can occur that is related with the collagenous tissues. ADAMTS3 mainly maturates type II collagen molecule which is the main component of the bone and cartilage. There are several expression studies about ADAMTS3 gene however its transcriptional regulation has not been lightened up, yet...
March 5, 2018: Gene
Xiang-Lei Chen, Yuan-Hua Cai, Qiao Liu, Li-Li Pan, Shui-Ling Shi, Xiao-Li Liu, Yuan Chen, Jing-Gang Li, Jing Wang, Yang Li, Xiao-Fan Li, Shao-Yuan Wang
DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501-bp region as the core promoter region of DHX15. Site-directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter...
March 7, 2018: Journal of Cellular and Molecular Medicine
De-Wei Wu, Yao-Chen Wang, Lee Wang, Chih Yi Chen, Huei Lee
Purpose: MicroRNA-630 plays dual roles in apoptosis and drug resistance in human cancers. However, the role of miR-630 in resistance to tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma remains to be elucidated. Methods: Manipulation of miR-630 and its targeted gene YAP1 and/or combination of inhibitor treatments was performed to explore whether low miR-630 could confer TKI resistance due to de-targeting YAP1, and this could decrease proapoptotic protein Bad expression through the miR-630/YAP1/ERK feedback loop...
2018: Theranostics
Sezen Karakus, Alan N Baer, Devika Agrawal, Merve Gurakar, Robert W Massof, Esen K Akpek
PURPOSE: To investigate the value of 3 novel autoantibodies [salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP)] in differentiating Sjögren's syndrome (SS)-related dry eye from non-SS dry eye. METHODS: Forty-six dry eye patients with SS (SS dry eye), 14 dry eye patients without SS (non-SS dry eye), and 25 controls were included. The 2012 American College of Rheumatology classification criteria were used for the diagnosis of SS...
April 2018: Cornea
Hyun-Kyung Kim, Mi Ae Kang, Mi-Sook Kim, Young-Joo Shin, Sung-Gil Chi, Jae-Hoon Jeong
High mobility group box 2 (HMGB2) is an abundant, chromatin-associated, non-histone protein involved in transcription, chromatin remodeling, and recombination. Recently, the HMGB2 gene was found to be significantly downregulated during senescence and shown to regulate the expression of senescent-associated secretory proteins. Here, we demonstrate that HMGB2 transcription is repressed by p21 during radiation-induced senescence through the ATM-p53-p21 DNA damage signaling cascade. The loss of p21 abolished the downregulation of HMGB2 caused by ionizing radiation, and the conditional induction of p21 was sufficient to repress the transcription of HMGB2...
February 28, 2018: Molecules and Cells
Carolina Becerril-Esquivel, Katia Peñuelas-Urquides, Erik Blancas-Sánchez, Pablo Zapata-Benavides, Beatriz Silva-Ramírez, Arturo Chávez-Reyes, Fabiola Castorena-Torres, Bulmaro Cisneros, Mario Bermúdez de León
The smallest product of the Duchenne muscular dystrophy gene, dystrophin (Dp)71, is ubiquitously expressed in nonmuscle tissues. We previously showed that Dp71 expression in hepatic cells is modulated in part by stimulating factor 1 (Sp1), stimulating protein 3 (Sp3), and yin yang 1 (YY1) transcription factors, and that the polyaromatic hydrocarbon, β-naphthoflavone (β‑NF), downregulates Dp71 expression. The aim of the present study was to determine whether β‑NF represses Dp71 expression by altering mRNA stability or its promoter activity...
February 21, 2018: Molecular Medicine Reports
Megha Amar, Birendra Nath Mallick
Rapid eye movement sleep (REMS) plays an important role in maintaining brain excitability by regulating noradrenaline (NA) level and Na-K ATPase activity. We showed earlier that REMS deprivation (REMSD) associated elevated NA increased neuronal, while decreased glial Na-K ATPase activity. However, our knowledge was insufficient on how the REMSD-associated effect is sustained particularly under chronic condition. Using Neuro-2a cells as a model, we investigated the molecular mechanism of NA-induced increase in mRNA expression of Na-K ATPase subunit and the enzyme activity...
February 22, 2018: Brain Research Bulletin
Yeo-Jung Kwon, Nam-Hyeon Cho, Dong-Jin Ye, Hyoung-Seok Baek, Yeon-Sang Ryu, Young-Jin Chun
Cytochrome P450 1B1 (CYP1B1), a well-known oncogene, has garnered wide attention because of its tumor-specific expression pattern and actions as a carcinogenic factor. Although CYP1B1 might play a crucial role in carcinogenesis, the detailed molecular mechanisms underlying oncogenic involvement in cancer development remain unclear. The present study investigated the manner in which CYP1B1 promotes survival of various cancer cells. Treatment with 2,2',4,6'-tetramethoxystilbene (TMS), a specific CYP1B1 inhibitor, significantly inhibited cell viability in human breast cancer and leukemia cell lines, including MCF-7, MDA-MB-231, HL-60, and U937 cells...
February 23, 2018: Journal of Toxicology and Environmental Health. Part A
Preethi Devanand, Yukiko Oya, Santhoshkumar Sundaramoorthy, Kye Yong Song, Tatsuro Watanabe, Yasuhito Kobayashi, Yoshihiko Shimizu, Soon Auck Hong, Masami Suganuma, In Kyoung Lim
To understand the regulation of Helicobacter pylori (H. pylori)-associated gastric carcinogenesis, we examined the effect of B-cell translocation gene 2 (BTG2) expression on the biological activity of Tipα, an oncoprotein secreted from H. pylori. BTG2, the human ortholog of mouse TIS21 (BTG2/TIS21 ), has been reported to be a primary response gene that is transiently expressed in response to various stimulations. Here, we report that BTG2 is constitutively expressed in the mucous epithelium and parietal cells of the gastric gland in the stomach...
February 23, 2018: Experimental & Molecular Medicine
Laleh Hakima, Kathie Schlesinger, Jaya Sunkara, Rouzan G Karabakhtsian
BACKGROUND: Women treated for breast cancer are at increased risk of developing pulmonary nodules which could represent new primary lung carcinomas or metastatic breast carcinoma. The FNA biopsy is frequently the first diagnostic choice in determining the primary site of the tumor. Estrogen receptor (ER) positivity in diagnostic tissue is generally used to favor breast over lung primary. However, the recent studies have shown a wide range of ER antibody cross reactivity with lung adenocarcinoma...
February 21, 2018: Diagnostic Cytopathology
Rulan Jiang, Bo Lönnerdal
Lactoferrin (Lf) is a major protein in human milk. Multiple biological functions of Lf are postulated to be mediated by a Lf receptor (LfR). The Lf receptor (LfR) plays an important role in absorption of Lf and Lf-bound iron by intestinal epithelial cells. Here, we cloned and characterized the promoter from a ~ 3.1 kb 5'-flanking region of the human LfR gene. Neither a TATA box nor a CCAAT box is found at the typical positions. The transcription start site was identified as 298 bp upstream of the translation start codon (+ 1) by 5' RLM-RACE...
February 20, 2018: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Rakshamani Tripathi, Leann S Fiore, Dana L Richards, Yuchen Yang, Jinpeng Liu, Chi Wang, Rina Plattner
The incidence of melanoma is increasing, particularly in young women, and the disease remains incurable for many because of its aggressive, metastatic nature and its high rate of resistance to conventional, targeted, and immunological agents. Cathepsins are proteases that are critical for melanoma progression and therapeutic resistance. Intracellular cathepsins cleave or degrade proteins that restrict cancer progression, whereas extracellular cathepsins directly cleave the extracellular matrix and activate proinvasive proteases in the tumor microenvironment...
February 20, 2018: Science Signaling
Fariba Boroumand, Hamideh Mahmoudinasab, Mostafa Saadat
BACKGROUND: Superoxide dismutase-2 (SOD2, OMIM: 147460) is involved in the detoxification of superoxide anions. The SOD2 mRNA level is down-regulated in cells exposed to morphine. Oxidative stress plays an important role in drug dependency. The rs2758339 (A/C) is located in the vicinity of SP1 and NF-κB transcription element sequences and the rs5746136 (A/G) creates a new glucocorticoid receptor binding site. Taken together, it is hypothesized that these polymorphisms might be associated with the risk of heroin dependency (HD) and the SOD2 expression level...
April 5, 2018: Gene
Qian Qian Cai, Yi Wei Dong, Bing Qi, Xiao-Ting Shao, Rong Wang, Zhong Yi Chen, Bao Mei He, Xing Zhong Wu
Integrin αV (ITGAV) gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and BRD1 (bromodomain containing protein 1) was identified as an interacting protein that also co-localized with sulfatide in HCC cells...
February 16, 2018: Molecular Cancer Research: MCR
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