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https://www.readbyqxmd.com/read/29040725/protein-s-nitrosylation-regulates-xylem-vessel-cell-differentiation-in-arabidopsis
#1
Harunori Kawabe, Misato Ohtani, Tetsuya Kurata, Tomoaki Sakamoto, Taku Demura
Post-translational modifications of proteins have important roles in the regulation of protein activity. One such modification, S-nitrosylation, involves the covalent binding of nitric oxide (NO)-related species to a cysteine residue. Recent work showed that protein S-nitrosylation has crucial functions in plant development and environmental responses. In the present study, we investigated the importance of protein S-nitrosylation for xylem vessel cell differentiation using a forward-genetics approach. We performed ethyl methanesulfonate mutagenesis of a transgenic Arabidopsis 35S::VND7-VP16-GR line in which the activity of VASCULAR-RELATED NAC-DOMAIN7 (VND7), a key transcription factor involved in xylem vessel cell differentiation, can be induced posttranslationally by glucocorticoid treatment, with the goal of obtaining suppressor mutants that failed to differentiate ectopic xylem vessel cells; we named these mutants suppressor of ectopic vessel cell differentiation induced by VND7 (seiv) mutants...
October 13, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/29040381/the-cug-translated-wt1-not-aug-wt1-is-an-oncogene
#2
Kun Yeong Lee, Young Jin Jeon, Hong Gyum Kim, Joohyun Ryu, Do Young Lim, Sung Keun Jung, Dong Hoon Yu, Hanyong Chen, Ann M Bode, Zigang Dong
The Wilms' tumor 1 (WT1) gene is believed to act as a canonical tumor suppressor. However, it has also been reported to function as an oncogene. Germline WT1 deletion is associated with Wilms' tumor and exogenous WT1 cDNA introduction into cells induces the transcriptional suppression of its oncogenic target genes. In contrast, high WT1 expression is associated with poor prognosis in patients with various cancers. Why WT1 acts as a tumor suppressor under certain conditions, but as an oncogene under other conditions is unknown...
October 10, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29036883/microrna-34a-a-versatile-regulator-of-myriads-of-targets-in-different-cancers
#3
REVIEW
Ammad Ahmad Farooqi, Sobia Tabassum, Aamir Ahmad
MicroRNA-34a (miR-34a) is a tumor suppressor that has attracted considerable attention in recent years. It modulates cancer cell invasion, metastasis, and drug resistance, and has also been evaluated as a diagnostic and/or prognostic biomarker. A number of targets of miR-34a have been identified, including some other non-coding RNAs, and it is believed that the modulation of these myriads of targets underlines the versatile role of miR-34a in cancer progression and pathogenesis. Seemingly appealing results from preclinical studies have advocated the testing of miR-34a in clinical trials...
October 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#4
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29036306/cxxc5-suppresses-hepatocellular-carcinoma-by-promoting-tgf-%C3%AE-induced-cell-cycle-arrest-and-apoptosis
#5
Xiaohua Yan, Jingyi Wu, Quanlong Jiang, Hao Cheng, Jing-Dong J Han, Ye-Guang Chen
Evading TGF-β-mediated growth inhibition is often associated with tumorigenesis in liver, including hepatocellular carcinoma (HCC). To better understand the functions and the underlying molecular mechanisms of TGF-β in HCC initiation and progression, we carried out transcriptome sequencing (RNA-Seq) to identify the target genes of TGF-β. CXXC5, a member of the CXXC-type zinc finger domain-containing protein family, was identified as a novel TGF-β target gene in Hep3B HCC cells. Knockdown of CXXC5 attenuated the expression of a substantial portion of TGF-β target genes and ameliorated TGF-β-induced growth inhibition or apoptosis of Hep3B cells, suggesting that CXXC5 is required for TGF-β-mediated inhibition of HCC progression...
September 19, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29036263/effects-of-12c6-heavy-ion-beam-irradiation-on-the-p53-signaling-pathway-in-hepg2-liver-cancer-cells
#6
Kai Liu, Xinke Zhao, Jing Gu, Jianjun Wu, Hong Zhang, Yingdong Li
The heavy ion beam is considered to be the ideal source for radiotherapy. The p53 tumor suppressor gene senses DNA damage and transducts intracellular apoptosis signals. Previous reports showed that the heavy ion beam can trigger complex forms of damage to cellular DNA, leading to cell cycle arrest and apoptosis of HepG2 human liver cancer cells; however, the mechanisms remains unclear fully. In order to explore whether the intrinsic or extrinsic pathway participates this process, HepG2 cells were treated with 12C6+ HIB irradiation at doses of 0 (control), 1, 2, 4, and 6 Gy with various methods employed to understand relevant mechanisms, such as detection of apoptosis, cell cycle, and Fas expression by flow cytometry, analysis of apoptotic morphology by electron microscopy and laser scanning confocal microscopy, and screening differentially expressed genes relating to p53 signaling pathway by PCR-array assay following with any genes confirmed by western blot analysis...
September 23, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29035909/dysregulated-myelopoiesis-and-hematopoietic-function-following-acute-physiologic-insult
#7
Tyler J Loftus, Alicia M Mohr, Lyle L Moldawer
PURPOSE OF REVIEW: The purpose of this review is to describe recent findings in the context of previous work regarding dysregulated myelopoiesis and hematopoietic function following an acute physiologic insult, focusing on the expansion and persistence of myeloid-deriver suppressor cells, the deterioration of lymphocyte number and function, and the inadequacy of stress erythropoiesis. RECENT FINDINGS: Persistent myeloid-derived suppressor cell (MDSC) expansion among critically ill septic patients is associated with T-cell suppression, vulnerability to nosocomial infection, chronic critical illness, and poor long-term functional status...
October 13, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29035445/expression-of-leukocytic-syncytin-1-in-b-cell-acute-lymphoblastic-leukemia-and-acute-myeloid-leukemia-patients
#8
Yi Sun, Hongyan Zhu, Jianxin Song, Yaxian Jiang, Hongmei Ouyang, Ting Dong, Rui Tao, Xin Fan, Guiqian Zhang
BACKGROUND: Syncytin-1 is improperly expressed in several cancers. However, its expression profile across leukocytes in leukemia patients has not yet been analyzed. METHODS: A total of 50 AML cases and 14 B-cell ALL patients were consecutively recruited. Bone marrow samples were subjected to flow cytometry. Statistical analysis was applied to compare syncytin-1 expression between B-cell ALL and AML across granulocytes, leukemia cells, and T-lymphocytes (including CD3+, CD4+, and CD8+ subsets thereof) and to correlate syncytin-1 expression to leukemia cells and lymphocytes with the T-cell subset percentages...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29035390/epigenetic-silencing-of-the-dual-role-signal-mediator-angptl4-in-tumor-tissues-and-its-overexpression-in-the-urothelial-carcinoma-microenvironment
#9
H-Y Hsieh, Y-C Jou, C-L Tung, Y-S Tsai, Y-H Wang, C-L Chi, R-I Lin, S-K Hung, Y-M Chuang, S-F Wu, C Li, C-H Shen, M W Y Chan, C-D Hsu
Urothelial carcinoma (UC) carcinogenesis has been hypothesized to occur through epigenetic repression of tumor-suppressor genes (TSGs). By quantitative real-time polymerase chain reaction array, we found that one potential TSG, angiopoietin-like 4 (ANGPTL4), was expressed at very low levels in all bladder cancer cell lines we examined. Previous studies had demonstrated that ANGPTL4 is highly expressed in some cancers, but downregulated, by DNA methylation, in others. Consequently, owing to these seemingly conflicting functions in distinct cancers, the precise role of ANGPTL4 in the etiology of UC remains unclear...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035389/-mcc-protein-interacts-with-e-cadherin-and-%C3%AE-catenin-strengthening-cell-cell-adhesion-of-hct116-colon-cancer-cells
#10
F A Benthani, D Herrmann, P N Tran, L Pangon, M C Lucas, A H Allam, N Currey, S Al-Sohaily, M Giry-Laterriere, J Warusavitarne, P Timpson, M R J Kohonen-Corish
E-cadherin and β-catenin are key proteins that are essential in the formation of the epithelial cell layer in the colon but their regulatory pathways that are disrupted in cancer metastasis are not completely understood. Mutated in colorectal cancer (MCC) is a tumour suppressor gene that is silenced by promoter methylation in colorectal cancer and particularly in patients with increased lymph node metastasis. Here, we show that MCC methylation is found in 45% of colon and 24% of rectal cancers and is associated with proximal colon, poorly differentiated, circumferential and mucinous tumours as well as increasing T stage and larger tumour size...
October 16, 2017: Oncogene
https://www.readbyqxmd.com/read/29035383/extracellular-nme-proteins-a-player-or-a-bystander
#11
Patrizia Romani, Marilena Ignesti, Giuseppe Gargiulo, Tien Hsu, Valeria Cavaliere
The Nm23/NME gene family has been under intensive study since Nm23H1/NME1 was identified as the first metastasis suppressor. Inverse correlation between the expression levels of NME1/2 and prognosis has indeed been demonstrated in different tumor cohorts. Interestingly, the presence of NME proteins in the extracellular environment in normal and tumoral conditions has also been noted. In many reported cases, however, these extracellular NME proteins exhibit anti-differentiation or oncogenic functions, contradicting their canonical anti-metastatic action...
October 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29034995/mir-1-suppresses-the-proliferation-and-promotes-the-apoptosis-of-esophageal-carcinoma-cells-by-targeting-src
#12
Zhicong Liao, Xiaojun Wang, Hongwei Liang, Ao Yu, Uzair Ur Rehman, Qian Fan, Yue Hu, Chen Wang, Zhen Zhou, Tao Wang
Nonreceptor tyrosine kinase c-Src, also known as Src, is a potent oncogene involved in a series of biological processes including cell growth, differentiation, and apoptosis; however, its expression pattern and function in esophageal cancer is poorly addressed. In this study, abnormal overexpression of Src protein was observed in esophageal cancer tissues, which fuelled the speculation that microRNA-mediated posttranscriptional regulatory mechanism might be involved. Bioinformatic analyses were applied to identify miRNAs that could potentially target Src...
October 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29034589/involvement-of-local-renin-angiotensin-system-in-immunosuppression-of-tumor-microenvironment
#13
Kenta Nakamura, Tomonori Yaguchi, Gaku Ohmura, Asuka Kobayashi, Naoshi Kawamura, Takashi Iwata, Yukiko Kiniwa, Ryuhei Okuyama, Yutaka Kawakami
To improve the current cancer immunotherapies, strategies to modulate various immunosuppressive cells including myeloid derived suppressor cells (MDSCs) which were shown to be negative factors in the immune-checkpoint blockade therapy, need to be developed. In this study, we have evaluated the role of local renin-angiotensin system (RAS) in the tumor immune-microenvironment using murine models bearing tumor cell lines in which RAS was not involved in their proliferation and angiogenetic ability. Administration of angiotensin II receptor blockers (ARBs) to C57BL/6 mice bearing murine colon cancer cell line MC38 resulted in significant enhancement of tumor antigen gp70 specific T cells...
October 16, 2017: Cancer Science
https://www.readbyqxmd.com/read/29034313/newly-characterized-murine-undifferentiated-sarcoma-models-sensitive-to-virotherapy-with-oncolytic-hsv-1-m002
#14
Eric K Ring, Rong Li, Blake P Moore, Li Nan, Virginia M Kelly, Xiaosi Han, Elizabeth A Beierle, James M Markert, Jianmei W Leavenworth, G Yancey Gillespie, Gregory K Friedman
Despite advances in conventional chemotherapy, surgical techniques, and radiation, outcomes for patients with relapsed, refractory, or metastatic soft tissue sarcomas are dismal. Survivors often suffer from lasting morbidity from current treatments. New targeted therapies with less toxicity, such as those that harness the immune system, and immunocompetent murine sarcoma models to test these therapies are greatly needed. We characterized two new serendipitous murine models of undifferentiated sarcoma (SARC-28 and SARC-45) and tested their sensitivity to virotherapy with oncolytic herpes simplex virus 1 (HSV-1)...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29033936/coinhibitory-receptor-expression-and-immune-checkpoint-blockade-maintaining-a-balance-in-cd8-t-cell-responses-to-chronic-viral-infections-and-cancer
#15
REVIEW
Isobel S Okoye, Michael Houghton, Lorne Tyrrell, Khaled Barakat, Shokrollah Elahi
In cancer and chronic viral infections, T cells are exposed to persistent antigen stimulation. This results in expression of multiple inhibitory receptors also called "immune checkpoints" by T cells. Although these inhibitory receptors under normal conditions maintain self-tolerance and prevent immunopathology, their sustained expression deteriorates T cell function: a phenomenon called exhaustion. Recent advances in cancer immunotherapy involve blockade of cytotoxic T lymphocyte antigen-4 and programmed cell death 1 in order to reverse T cell exhaustion and reinvigorate immunity, which has translated to dramatic clinical remission in many cases of metastatic melanoma and lung cancer...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29033588/hoxd-as1-functions-as-an-oncogenic-cerna-to-promote-nsclc-cell-progression-by-sequestering-mir-147a
#16
Qinghua Wang, Shujun Jiang, Anying Song, Siyuan Hou, Qinfeng Wu, Longju Qi, Xiang Gao
Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and it occurs at a higher frequency in males. HOXD-AS1, an important cancer-associated long noncoding RNA (lncRNA), contributes to the development and progression of several cancers. However, the exact roles of HOXD-AS1 in NSCLC progression are still unknown. Here, we investigated the underlying mechanisms of HOXD-AS1 in human NSCLC tissues. We found that lncRNA HOXD-AS1 was specifically upregulated (P<0.001) in NSCLC tissues and promoted cancer cell growth by targeting miR-147a...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29033353/melanocyte-stem-cell-activation-and-translocation-initiate-cutaneous-melanoma-in-response-to-uv-exposure
#17
Hyeongsun Moon, Leanne R Donahue, Eunju Choi, Philip O Scumpia, William E Lowry, Jennifer K Grenier, Jerry Zhu, Andrew C White
Melanoma is one of the deadliest cancers, yet the cells of origin and mechanisms of tumor initiation remain unclear. The majority of melanomas emerge from clear skin without a precursor lesion, but it is unknown whether these melanomas can arise from melanocyte stem cells (MCSCs). Here we employ mouse models to define the role of MCSCs as melanoma cells of origin, demonstrate that MCSC quiescence acts as a tumor suppressor, and identify the extrinsic environmental and molecular factors required for the critical early steps of melanoma initiation...
October 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/29033320/mitophagy-controls-the-activities-of-tumor-suppressor-p53-to-regulate-hepatic-cancer-stem-cells
#18
Kai Liu, Jiyoung Lee, Ja Yeon Kim, Linya Wang, Yongjun Tian, Stephanie T Chan, Cecilia Cho, Keigo Machida, Dexi Chen, Jing-Hsiung James Ou
Autophagy is required for benign hepatic tumors to progress into malignant hepatocellular carcinoma. However, the mechanism is unclear. Here, we report that mitophagy, the selective removal of mitochondria by autophagy, positively regulates hepatic cancer stem cells (CSCs) by suppressing the tumor suppressor p53. When mitophagy is enhanced, p53 co-localizes with mitochondria and is removed by a mitophagy-dependent manner. However, when mitophagy is inhibited, p53 is phosphorylated at serine-392 by PINK1, a kinase associated with mitophagy, on mitochondria and translocated into the nucleus, where it binds to the NANOG promoter to prevent OCT4 and SOX2 transcription factors from activating the expression of NANOG, a transcription factor critical for maintaining the stemness and the self-renewal ability of CSCs, resulting in the reduction of hepatic CSC populations...
October 10, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29032490/myeloid-derived-suppressor-cells-in-the%C3%A2-tumor-microenvironment-current-knowledge-and-future-perspectives
#19
REVIEW
Maria Ibáñez-Vea, Miren Zuazo, Maria Gato, Hugo Arasanz, Gonzalo Fernández-Hinojal, David Escors, Grazyna Kochan
The current knowledge on tumor-infiltrating myeloid-derived suppressor cells (MDSCs) is based mainly on the extensive work performed in murine models. Data obtained for human counterparts are generated on the basis of tumor analysis from patient samples. Both sources of information led to determination of the main suppressive mechanisms used by these cell subsets in tumor-bearing hosts. As a result of the identification of protein targets responsible for MDSCs suppressive activity, different therapeutics agents have been used to eliminate/reduce their adverse effect...
October 14, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/29032337/mir-758-3p-suppresses-proliferation-migration-and-invasion-of-hepatocellular-carcinoma-cells-via-targeting-mdm2-and-mtor
#20
Dan Jiang, William Cho, Zhenhao Li, Xiangrong Xu, Yuliang Qu, Zhongjia Jiang, Le Guo, Guangxian Xu
Hepatocelluar carcinoma (HCC) is one of the most frequently diagnosed cancers worldwide and among the leading causes of cancer-related death. Although deregulation of microRNAs has been frequently described in HCC, imperfection is known about the precise molecular mechanisms by which microRNAs modulate the process of tumorogenesis and behavior of cancer cells. In this study, we demonstrated that miR-758-3p could suppress cell proliferation, migration and invasion in hepatocellular carcinoma cells. We screened and identified two novel miR-758-3p targets, MDM2 and mTOR...
October 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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