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https://www.readbyqxmd.com/read/28734980/histone-demethylase-phf8-regulates-hypoxia-signaling-through-hif1%C3%AE-and-h3k4me3
#1
Peterson Kariuki Maina, Peng Shao, Xiongfei Jia, Qi Liu, Shaikamjad Umesalma, Maximo Marin, Donald Long, Samantha Concepción-Román, Hank Heng Qi
Hypoxia through transcription factor HIF1α plays a critical role in cancer development. In prostate cancer, HIF1α interplays with androgen receptor (AR) to contribute to the progression of this disease to its lethal form-castration-resistant prostate cancer (CRPC). Hypoxia upregulates several epigenetic factors including histone demethylase KDM3A which is a critical co-factor of HIF1α. However, how histone demethylases regulate hypoxia signaling is not fully understood. Here, we report that histone demethylase PHF8 plays an essential role in hypoxia signaling...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#2
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730444/oxime-ether-lipids-as-transfection-agents-assembly-and-complexation-with-sirna
#3
Anu Puri, Serena Zampino, Mathias Viard, Bruce A Shapiro
RNAi-based therapeutic approaches to combat cancer and other diseases are currently an area of great interest. However, practical applications of this approach rely on optimal tools to carry and deliver siRNA to the desired site. Oxime ether lipids (OELs) are a class of molecules among other various carriers being examined for siRNA delivery. OELs, relatively new candidates, belong to a class of non-glycerol based lipids and have begun to claim their place as an siRNA delivery carrier in the field of RNAi therapy...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730440/cellular-delivery-of-sirnas-using-bolaamphiphiles
#4
Kshitij Gupta
Discovery of RNA interference (RNAi) has opened up a new arena of therapeutic intervention for the treatment of cancerous as well as noncancerous diseases. The RNAi pathway utilizes RNAi inducers such as small interfering RNAs (siRNAs) to target and silence disease causing genes. However, efficient delivery of siRNAs for eliciting efficacious RNAi has remained a daunting challenge. Nonviral vectors such as lipids have shown great promise in delivering siRNAs. Recently, a novel class of cationic lipid molecules "bolaamphiphile lipids" or "bola lipids" has been shown to deliver siRNAs to cause effective gene silencing in cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28724889/aptamer-mediated-survivin-rnai-enables-5-fluorouracil-to-eliminate-colorectal-cancer-stem-cells
#5
Hadi AlShamaileh, Tao Wang, Dongxi Xiang, Wang Yin, Phuong Ha-Lien Tran, Roberto A Barrero, Pei-Zhuo Zhang, Yong Li, Lingxue Kong, Ke Liu, Shu-Feng Zhou, Yingchun Hou, Sarah Shigdar, Wei Duan
The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724888/crosscheck-an-open-source-web-tool-for-high-throughput-screen-data-analysis
#6
Jamil Najafov, Ayaz Najafov
Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717185/clinical-significance-and-effect-of-lncrna-hoxa11-as-in-nsclc-a-study-based-on-bioinformatics-in-vitro-and-in-vivo-verification
#7
Yu Zhang, Wen-Jie Chen, Ting-Qing Gan, Xiu-Ling Zhang, Zu-Cheng Xie, Zhi-Hua Ye, Yun Deng, Ze-Feng Wang, Kai-Teng Cai, Shi-Kang Li, Dian-Zhong Luo, Gang Chen
HOXA11 antisense RNA (HOXA11-AS) has been shown to be involved in tumorigenesis and development of different cancers. However, the role of HOXA11-AS in non-small cell lung cancer (NSCLC) remains unclear. In this study, we firstly explored and confirmed the expression of HOXA11-AS in NSCLC tissues and cells. Cytometry, CCK-8, cell scratch, migration, Matrigel invasion and flow cytometry assays were performed to determine the biological impact of HOXA11-AS in vitro. Furthermore, a chick embryo chorioallantoic membrane (CAM) model of NSCLC was constructed to explore the effect of HOXA11-AS on tumorigenicity and angiogenesis in vivo...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710230/the-tissue-reconstructing-ability-of-colon-cscs-is-enhanced-by-fk506-and-suppressed-by-gsk3-inhibition
#8
Ryo Ishida, Michiyo Koyanagi-Aoi, Nobu Oshima, Yoshihiro Kakeji, Takashi Aoi
Cancer stem cells (CSCs) are capable of reconstructing cancer tissues, are involved in both recurrence and metastasis, and contribute to therapeutic resistance. Therefore, elucidating the molecular mechanism in CSCs is important to successfully treat unresectable cancers. Previously we observed that colon cancer stem-like cells can be induced from human colon cancer cell lines by retrovirally introducing OCT3/4, SOX2 and KLF4, and we have designated such cells as induced cancer stem cells (iCSCs). In the current study, we used iCSCs to evaluate the molecular mechanism of colon CSCs and developed new methods to control them...
July 14, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28692053/pre-45s-rrna-promotes-colon-cancer-and-is-associated-with-poor-survival-of-crc-patients
#9
H Tsoi, K C Lam, Y Dong, X Zhang, C K Lee, J Zhang, S C Ng, S S M Ng, S Zheng, Y Chen, J Fang, J Yu
One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28689100/synthesis-and-characterization-of-amino-acid-functionalized-calcium-phosphate-nanoparticles-for-sirna-delivery
#10
Feray Bakan, Goknur Kara, Melike Cokol Cakmak, Murat Cokol, Emir Baki Denkbas
Small interfering RNAs (siRNA) are short nucleic acid fragments of about 20-27 nucleotides, which can inhibit the expression of specific genes. siRNA based RNAi technology has emerged as a promising method for the treatment of a variety of diseases. However, a major limitation in the therapeutic use of siRNA is its rapid degradation in plasma and cellular cytoplasm, resulting in short half-life. In addition, as siRNA molecules cannot penetrate into the cell efficiently, it is required to use a carrier system for its delivery...
June 27, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28687017/methylation-of-bnip3-in-pancreatic-cancer-inhibits-the-induction-of-mitochondrial-mediated-tumor-cell-apoptosis
#11
Ye Li, Xu Zhang, Jian Yang, Yi Zhang, Dongming Zhu, Lifeng Zhang, Yanbo Zhu, Dechun Li, Jian Zhou
Bcl-2 interacting protein 3 (BNIP3) is involved in various cellular processes and is considered a key regulator of hypoxia-induced apoptosis. In the present study, the expression of BNIP3 in pancreatic cancer tissues, the correlation with clinicopathological characteristics and prognosis and the regulation of this protein in pancreatic cancer cell lines with regard to the induction of apoptosis were investigated. BNIP3 expression was significantly lower in pancreatic cancer tissues compared with normal epithelia and was associated with tumor size, clinical stage, and lymph node metastasis...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28684168/rnai-prodrugs-targeting-plk1-induce-specific-gene-silencing-in-primary-cells-from-pediatric-t-acute-lymphoblastic-leukemia-patients
#12
Iryna Kolosenko, Elin Edsbäcker, Ann-Charlotte Björklund, Alexander S Hamil, Oksana Goroshchuk, Dan Grandér, Steven F Dowdy, Caroline Palm-Apergi
Epidemiological studies of childhood leukemia survivors reveal an alarmingly high incidence of chronic health disabilities after treatment, therefore, more specific therapies need to be developed. Polo-like kinase 1 (Plk1) is a key player in mitosis and a target for drug development as it is upregulated in multiple cancer types. Small molecules targeting Plk1 are mainly ATP-competitors and, therefore, are known to elicit side effects due to lack of specificity. RNA interference (RNAi) is known for its high catalytic activity and target selectivity; however, the biggest barrier for its introduction into clinical use is its delivery...
July 3, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28680435/molecular-characterization-of-myb28-involved-in-aliphatic-glucosinolate-biosynthesis-in-chinese-kale-brassica-oleracea-var-alboglabra-bailey
#13
Ling Yin, Hancai Chen, Bihao Cao, Jianjun Lei, Guoju Chen
Glucosinolates are Brassicaceae-specific secondary metabolites that act as crop protectants, flavor precursors, and cancer-prevention agents, which shows strong evidences of anticarcinogentic, antioxidant, and antimicrobial activities. MYB28, the R2R3-MYB28 transcription factor, directly activates genes involved in aliphatic glucosinolate biosynthesis. In this study, the MYB28 homology (BoaMYB28) was identified in Chinese kale (Brassica oleracea var. alboglabra Bailey). Analysis of the nucleotide sequence indicated that the cDNA of BoaMYB28 was 1257 bp with an ORF of 1020 bp...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28680090/pan-cancer-emt-signature-identifies-rbm47-down-regulation-during-colorectal-cancer-progression
#14
Matjaz Rokavec, Markus Kaller, David Horst, Heiko Hermeking
Epithelial-mesenchymal transition (EMT) plays an important role in tumor invasion and metastasis. A comprehensive, bioinformatics analysis of CCLE and TCGA datasets of seven tumor types allowed us to identify a novel pan-cancer EMT-associated gene expression signature consisting of 16 epithelial and 4 mesenchymal state-associated mRNAs. Among the identified epithelial cell state-associated factors, down-regulation of the RBM47 (RNA binding motif protein 47) mRNA displayed the most significant association with metastasis and poor survival in multiple cohorts of colorectal cancer (CRC) patients...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28678782/transcription-elongation-factors-represent-in-vivo-cancer-dependencies-in-glioblastoma
#15
Tyler E Miller, Brian B Liau, Lisa C Wallace, Andrew R Morton, Qi Xie, Deobrat Dixit, Daniel C Factor, Leo J Y Kim, James J Morrow, Qiulian Wu, Stephen C Mack, Christopher G Hubert, Shawn M Gillespie, William A Flavahan, Thomas Hoffmann, Rohit Thummalapalli, Michael T Hemann, Patrick J Paddison, Craig M Horbinski, Johannes Zuber, Peter C Scacheri, Bradley E Bernstein, Paul J Tesar, Jeremy N Rich
Glioblastoma is a universally lethal cancer with a median survival time of approximately 15 months. Despite substantial efforts to define druggable targets, there are no therapeutic options that notably extend the lifespan of patients with glioblastoma. While previous work has largely focused on in vitro cellular models, here we demonstrate a more physiologically relevant approach to target discovery in glioblastoma. We adapted pooled RNA interference (RNAi) screening technology for use in orthotopic patient-derived xenograft models, creating a high-throughput negative-selection screening platform in a functional in vivo tumour microenvironment...
July 5, 2017: Nature
https://www.readbyqxmd.com/read/28677774/construction-of-a-recombinant-lentivirus-mediated-shrna-expression-vector-targeting-the-human-psmd10-gene-and-validation-of-rnai-efficiency-in-rpmi%C3%A2-8226-multiple-myeloma-cells
#16
Siyue Du, Wenjiao Qin, Haiyan Leng, Zi Chen, Tao Zhang
Multiple myeloma (MM) is one of the most common malignant blood cancers. Previous studies have reported that proteasome 26S subunit non-ATPase 10 (PSMD10) is an oncoprotein with complex roles in hepatocellular carcinoma and other malignant tumors. Notably, research on the relationship between PSMD10 and tumorigenesis of MM has rarely been reported. The present study was designed to explore the possibility of PSMD10 as a therapeutic target in the treatment of MM, and the use of RNA interference (RNAi) to determine the function PSMD10...
June 30, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28674811/a-phenotype-based-rnai-screening-for-ras-erk-mapk-signaling-associated-stem-cell-regulators-in-c-elegans
#17
Myon-Hee Lee, Dong Suk Yoon
Stem cells have the ability to self-renew and to generate differentiated cell types. A regulatory network that controls this balance is critical for stem cell homeostasis and normal animal development. Particularly, Ras-ERK/MAPK signaling pathway is critical for stem cell self-renewal and differentiation in mammals, including humans. Aberrant regulation of Ras-ERK/MAPK signaling pathway results in either stem cell or overproliferation. Therefore, the identification of Ras-ERK/MAPK signaling pathway-associated regulators is critical to understand the mechanism of stem cell (possibly cancer stem cell) control...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674799/forward-rnai-screens-in-human-hematopoietic-stem-cells
#18
Roman Galeev, Christine Karlsson, Aurélie Baudet, Jonas Larsson
Identifying the genes and pathways that regulate self-renewal and differentiation in somatic stem cells is a central goal in stem cell and cancer biology. Here, we describe a method for RNA interference (RNAi)-based screens combined with next-generation sequencing (NGS) in primary human hematopoietic stem and progenitor cells (HSPCs). These cells are suitable targets for complex, selection-based screens using pooled lentiviral short hairpin RNA (shRNA) libraries. The screening approach presented in this chapter is a promising tool to dissect regulatory mechanisms in hematopoietic stem cells (HSCs) and somatic stem cells in general, and may be particularly useful to identify gene targets and modifiers that can be further exploited in strategies for ex vivo stem cell expansion...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28674797/rnai-technique-in-stem-cell-research-current-status-and-future-perspectives
#19
Gang-Ming Zou
RNAi is a mechanism displayed by most eukaryotic cells to rid themselves of foreign double-strand RNA molecules. In the 18 years since the initial report, RNAi has now been demonstrated to function in mammalian cells to alter gene expression and has been used as a means for genetic discovery as well as a possible strategy for genetic correction and genetic therapy in cancer and other disease. The aim of this review is to provide a general overview of how RNAi suppresses gene expression and to examine some published RNAi approaches that have resulted in changes in stem cell function and suggest the possible clinical relevance of this work in cancer therapy through targeting cancer stem cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28670367/silencing-of-advanced-glycosylation-and-glycosylation-and-product-specific-receptor-rage-inhibits-the-metastasis-and-growth-of-non-small-cell-lung-cancer
#20
Yan Xia Yu, Wen Chong Pan, Yu Feng Cheng
Non-small cell lung cancer (NSCLC) constitutes the main cases of lung cancer and is the world's most common and lethal cancer owing to regional invasion or distant metastasis. Growing morbidity and lethality demonstrates that valid molecular target in management of NSCLC metastasis is still absence. The receptor of advanced glycation end-products (RAGE) has been identified as an oncogenic gene and appears to promote the growth and metastasis of various cancers. Here, we investigated if RAGE targeted by RNA interference (RNAi) might have certain effect on the restraint of the growth of NSCLC and tumor metastasis...
2017: American Journal of Translational Research
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