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https://www.readbyqxmd.com/read/29673664/high-throughput-silencing-identifies-novel-genes-in-endometrioid-endometrial-cancer
#1
Afiqah Alyaa Md Fuzi, Siti Zawiah Omar, Zahurin Mohamed, Noor Azmi Mat Adenan, Norfilza Mohd Mokhtar
OBJECTIVE: To validate the gene expression profile obtained from the previous microarray analysis and to further study the biological functions of these genes in endometrial cancer. From our previous study, we identified 621 differentially expressed genes in laser-captured microdissected endometrioid endometrial cancer as compared to normal endometrial cells. Among these genes, 146 were significantly up-regulated in endometrial cancer. MATERIALS AND METHODS: A total of 20 genes were selected from the list of up-regulated genes for the validation assay...
April 2018: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29662165/deconvolution-of-seed-and-rna-binding-protein-crosstalk-in-rnai-based-functional-genomics
#2
Hiroshi I Suzuki, Ryan M Spengler, Giedre Grigelioniene, Tatsuya Kobayashi, Phillip A Sharp
RNA interference (RNAi) is a major, powerful platform for gene perturbations, but is restricted by off-target mechanisms. Communication between RNAs, small RNAs, and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks. We present a crosstalk scenario, designated as crosstalk with endogenous RBPs' (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing endogenous RBP activity. Systematic analysis of small interfering RNA (siRNA) off-target data and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines, a cancer dependency map, identified that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance...
April 16, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29656061/hypoxia-inducible-bidirectional-shrna-expression-vector-delivery-using-pei-chitosan-tba-copolymers-for-colorectal-cancer-gene-therapy
#3
Bita Javan, Fatemeh Atyabi, Majid Shahbazi
AIMS: This investigation was conducted to construct a hypoxia/colorectal dual-specific bidirectional short hairpin RNA (shRNA) expression vector and to transfect it into the colon cancer cell line HT-29 with PEI/chitosan-TBA nanoparticles for the simultaneous knock down of β-catenin and Bcl-2 under hypoxia. MAIN METHODS: To construct a pRNA-bipHRE-CEA vector, the carcinoma embryonic antigen (CEA) promoter designed in two directions and the vascular endothelial growth factor (VEGF) enhancer were inserted between two promoters for hypoxic cancer specific gene expression...
April 12, 2018: Life Sciences
https://www.readbyqxmd.com/read/29628790/heme-oxygenase-inhibition-in-cancers-possible-tools-and-targets
#4
REVIEW
Paulina Podkalicka, Olga Mucha, Alicja Józkowicz, Józef Dulak, Agnieszka Łoboda
Heme oxygenase-1 (HO-1, encoded by HMOX1 ) through degradation of pro-oxidant heme into carbon monoxide (CO), ferrous ions (Fe2+ ) and biliverdin, exhibits cytoprotective, anti-apoptotic and anti-inflammatory properties. All of these potentially beneficial functions of HO-1 may play an important role in tumors' development and progression. Moreover, HO-1 is very often upregulated in tumors in comparison to healthy tissues, and its expression is further induced upon chemo-, radio- and photodynamic therapy, what results in decreased effectiveness of the treatment...
March 2018: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/29625201/sarnadb-resource-of-small-activating-rnas-for-up-regulating-the-gene-expression
#5
Showkat Ahmad Dar, Manoj Kumar
RNA activation (RNAa) is the process of enhancing selective gene expression at transcriptional level using double stranded RNAs, targeting gene promoter. These RNA molecules are usually twenty-one nucleotides long and termed as small activating RNAs (saRNAs). They are involved in gene regulation, epigenetics gain-of-function studies and as have potential therapeutic application for various diseases especially cancer. RNAa is opposite to RNA interference (RNAi) in functionality however; both processes share some protein machinery...
April 3, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29624814/eif2%C3%AE-a-subunit-of-translation-initiation-factor-eif2-is-a-potential-therapeutic-target-for-non-small-cell-lung-cancer
#6
Ichidai Tanaka, Mitsuo Sato, Toshio Kato, Daiki Goto, Tomohiko Kakumu, Ayako Miyazawa, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Yoshitaka Sekido, Luc Girard, John D Minna, Lauren A Byers, John V Heymach, Kevin R Coombes, Masashi Kondo, Yoshinori Hasegawa
To identify novel therapeutic targets for non-small cell lung cancer (NSCLC), we conducted an integrative study in the following three stages: (1) identification of potential target gene(s) through shRNA functional screens in two independent NSCLC cell lines, (2) validation of the clinical relevance of identified gene(s) using public databases, and (3) investigation of therapeutic potential of targeting the identified gene(s) in vitro. A semi-genome wide shRNA screen was performed in NCI-H358 cells, and was integrated with data from our previous screen in NCI-H460 cells...
April 6, 2018: Cancer Science
https://www.readbyqxmd.com/read/29621396/reversal-of-ovarian-cancer-multidrug-resistance-by-a-combination-of-lah4-l1-simdr1-nanocomplexes-with-chemotherapeutics
#7
Nana Guo, Chen Gao, Jing Liu, Jun Li, Nan Liu, Yanli Hao, Lei Chen, Xiaoning Zhang
The mortality of ovarian cancer stably ranks first in gynecological malignancies due to the lack of specific symptoms and diagnostic methods at an early stage. For most patients, the cancer cells had metastasized before they were diagnosed. As a result 90% of them died of multidrug resistance to chemotherapeutics. In our study, RNAi technology was introduced and applied to overcome this big problem. LAH4-L1, an amphipathic cationic polypeptide, was reported to have high transfection efficiency and was firstly selected by us to deliver siMDR1 for overcoming ovarian cancer cells MDR...
April 5, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29611475/gene-silencing-strategies-in-cancer-therapy-an-update-for-drug-resistance
#8
Sanaz Naghizadeh, Behzad Mansoori, Ali Mohammadi, Sakhinia Ebrahim, Behzad Baradaran
RNAi, post-transcriptional gene silencing mechanism, could be considered as one of the most important breakthroughs and rapidly growing fields in science. Researchers are trying to use this discovery in the treatment of various diseases and cancer is one of them. Multiple treatment procedures for treatments-resistance cancers remain as unsolvable problem yet. The current review summarizes both transcriptional and post-transcriptional gene silencing mechanisms, and highlights mechanisms leading to drug-resistance such as, drug efflux, drug inactivation, drug target alteration, DNA damages repair, and the epithelial-mesenchymal transition, as well as the role of tumor cell heterogeneity and tumor microenvironment, involved genes in these processes...
April 3, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29601972/complexation-of-chol-dsirna-in-place-of-chol-sirna-greatly-increases-the-duration-of-mrna-suppression-by-polyplexes-of-pll-30-peg-5k-in-primary-murine-syngeneic-breast-tumors-after-i-v-administration
#9
Vishakha V Ambardekar, Rajesh R Wakaskar, Zhen Ye, Stephen M Curran, Timothy R McGuire, Don W Coulter, Rakesh K Singh, Joseph A Vetro
RNA interference has tremendous potential for cancer therapy but is limited by the insufficient potency of RNAi molecules after i.v. administration. We previously found that complexation with PLL(30)-PEG(5K) greatly increases the potency of 3'-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic 4T1 breast tumors after i.v. administration but mRNA suppression decreases 24 hours after the final dose. We hypothesized that complexation of cholesterol-modified Dicer-substrate siRNA (Chol-DsiRNA) in place of Chol-siRNA can increase the potency and duration of suppression by polyplexes of PLL(30)-PEG(5K) in solid tumors...
March 27, 2018: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29600769/anti-cancer-effect-of-%C3%A9-solanine-mainly-by-down-regulating-s100p-expression-in-colorectal-cancer-cells
#10
Xiaofen Ni, Jiajun Chen, Fengying Lu, Zhengzhong Yuan, Xiaofeng Xu, Zhen Hu, Lei Jiang
BACKGROUND: ɑ-Solanine, the most important and active component of Solanum nigrum, was found to have anti-cancer activity on multiple cancer cells. However, its effects on colorectal cancer (CRC) and associated molecular mechanisms remain to be further elucidated. OBJECTIVE: In this study, we investigated the anti-cancer effects of ɑ-solanine against CRC cells in vitro and in vivo. METHOD: Cell viability was measured using Cell Counting Kit-8 (CCK-8) assay; cell cycle was analyzed with a Cycletest Plus DNA Reagent Kit; cell apoptosis was detected by flow cytometry; cell migration and invasive ability was determined by Transwell assays; S100P protein expression was also analyzed by western blotting; lentiviral vectors expressing shRNA targeting the S100P gene...
March 29, 2018: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/29600377/rna-interference-mediated-gene-silencing-in-esophageal-adenocarcinoma
#11
Farhadul Islam, Vinod Gopalan, Alfred K Lam
RNA interference (RNAi) is a normal physiological mechanism in which a short effector antisense RNA molecule regulates target gene expression. It is a powerful tool to silence a particular gene of interest in a sequence-specific manner and can be used to target against various molecular pathways in esophageal adenocarcinoma by designing RNAi targeting key pathogenic genes. RNAi-based therapeutics against esophageal adenocarcinoma can be developed using different strategies including inhibition of overexpressed oncogenes, blocking cell division by interfering cyclins and related genes or enhancing apoptosis by suppressing anti-apoptotic genes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29569755/ldha-is-a-direct-target-of-mir-30d-5p-and-contributes-to-aggressive-progression-of-gallbladder-carcinoma
#12
Yuting He, Xiaolong Chen, Yan Yu, Juan Li, Qiuyue Hu, Chen Xue, Jianan Chen, Shen Shen, Yonggang Luo, Fang Ren, Chao Li, Jie Bao, Jingya Yan, Guowu Qian, Zhigang Ren, Ranran Sun, Guangying Cui
Gallbladder cancer (GBC) is the most general biliary tract malignancy, with poor prognosis due to rapid tumor progression and lack of specific symptoms. Lactate dehydrogenase-A (LDHA) can promote Warburg effect to produce lactate and Adenosine Triphosphate (ATP) in aerobic condition, which contributes to oncogenesis metastasis and drug resistance in various cancers. However, the expression and functional role of LDHA in GBC are largely unknown. We determined that LDHA was over-expressed in GBC tumor tissues compared with normal tissues, which was also an independent prognostic factor for the overall survival of GBC patients by tissue microarrays analysis...
March 23, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29565554/a-complementary-chemical-and-genomic-screening-approach-for-druggable-targets-in-the-nrf2-pathway-and-small-molecule-inhibitors-to-overcome-cancer-cell-drug-resistance
#13
James H Matthews, Xiao Liang, Valerie J Paul, Hendrik Luesch
Resistance to chemotherapy is a major obstacle in the treatment of a wide array of different types of cancer. Chemotherapeutic drug resistance is achieved by cancer cells by a variety of different mechanisms, which can be either compound specific or general. An emerging mechanism for nonspecific chemotherapeutic drug resistance relies on hyperactivity of the transcription factor Nrf2. Normally Nrf2 levels are tightly regulated by the ubiquitin-proteasome system; however, mutations in genes responsible for this regulation are common in many cancer types, resulting in increased expression of Nrf2, activation of its downstream target genes, and resistance to a variety of chemotherapeutic agents...
March 22, 2018: ACS Chemical Biology
https://www.readbyqxmd.com/read/29565490/wnt3-knockdown-sensitizes-human-non-small-cell-type-lung-cancer-nsclc-cells-to-cisplatin-via-regulating-the-cell-proliferation-and-apoptosis
#14
Z Xing, H-Y Wang, W-Y Su, Y-F Liu, X-X Wang, P Zhan, T-F Lv, Y Song
OBJECTIVE: Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/β-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer. PATIENTS AND METHODS: Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated...
March 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29561622/lipid-based-liquid-crystalline-nanoparticles-facilitate-cytosolic-delivery-of-sirna-via-structural-transformation
#15
Shufang He, Weiwei Fan, Na Wu, Jingjing Zhu, Yunqiu Miao, Xiaran Miao, Feifei Li, Xinxin Zhang, Yong Gan
RNA interference (RNAi) technology has shown great promise for the treatment of cancer and other genetic disorders. Despite the efforts to increase the target tissue distribution, the safe and effective delivery of siRNA to the diseased cells with sufficient cytosolic transport is another critical factor for successful RNAi clinical application. Here, the constructed lipid-based liquid crystalline nanoparticles, called nano-Transformers, can transform the structure in the intracellular acidic environment, and perform high-efficient siRNA delivery for cancer treatment...
March 21, 2018: Nano Letters
https://www.readbyqxmd.com/read/29559670/identification-of-di-substituted-ureas-that-prevent-growth-of-trypanosomes-through-inhibition-of-translation-initiation
#16
Fabricio Castro Machado, Caio Haddad Franco, Jose Vitorino Dos Santos Neto, Karina Luiza Dias-Teixeira, Carolina Borsoi Moraes, Ulisses Gazos Lopes, Bertal Huseyin Aktas, Sergio Schenkman
Some 1,3-diarylureas and 1-((1,4-trans)-4-aryloxycyclohexyl)-3-arylureas (cHAUs) activate heme-regulated kinase causing protein synthesis inhibition via phosphorylation of the eukaryotic translation initiation factor 2 (eIF2) in mammalian cancer cells. To evaluate if these agents have potential to inhibit trypanosome multiplication by also affecting the phosphorylation of eIF2 alpha subunit (eIF2α), we tested 25 analogs of 1,3-diarylureas and cHAUs against Trypanosoma cruzi, the agent of Chagas disease. One of them (I-17) presented selectivity close to 10-fold against the insect replicative forms and also inhibited the multiplication of T...
March 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29549271/imaging-of-conditional-gene-silencing-in-vivo-using-a-bioluminescence-based-method-with-thermo-inducible-micrornas
#17
Karine Pinel, Coralie Genevois, Christelle Debeissat, Franck Couillaud
RNA interference (RNAi)-based gene therapy has great potential in cancer and infectious disease treatment to correct abnormal up-regulation of gene expression. We show a new original method uses synthetic microRNAs combined with a thermo-inducible promoter to reduce specific gene expression. The targeted gene is the luciferase firefly reporter gene overexpressed in a subcutaneous tumor which allows the RNAi monitoring by bioluminescence imaging (BLI). The inducible inhibition was first demonstrated in vitro using genetically modified cells lines and then in vivo using the corresponding xenograft model in mice...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29549256/plk1-has-tumor-suppressive-potential-in-apc-truncated-colon-cancer-cells
#18
Monika Raab, Mourad Sanhaji, Yves Matthess, Albrecht Hörlin, Ioana Lorenz, Christina Dötsch, Nils Habbe, Oliver Waidmann, Elisabeth Kurunci-Csacsko, Ron Firestein, Sven Becker, Klaus Strebhardt
The spindle assembly checkpoint (SAC) acts as a molecular safeguard in ensuring faithful chromosome transmission during mitosis, which is regulated by a complex interplay between phosphatases and kinases including PLK1. Adenomatous polyposis coli (APC) germline mutations cause aneuploidy and are responsible for familial adenomatous polyposis (FAP). Here we study the role of PLK1 in colon cancer cells with chromosomal instability promoted by APC truncation (APC-ΔC). The expression of APC-ΔC in colon cells reduces the accumulation of mitotic cells upon PLK1 inhibition, accelerates mitotic exit and increases the survival of cells with enhanced chromosomal abnormalities...
March 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29545475/olaparib-induced-adaptive-response-is-disrupted-by-foxm1-targeting-which-enhances-sensitivity-to-parp-inhibition
#19
Pingping Fang, Jill A Madden, Lisa Neums, K Ryan Moulder, M Laird Forrest, Jeremy Chien
FOXM1 transcription factor network is activated in over 84% of cases in high-grade serous ovarian cancer (HGSOC), and FOXM1 upregulates the expression of genes involved in the homologous recombination (HR) DNA damage and repair (DDR) pathway. However, the role of FOXM1 in poly (ADP-ribose) polymerase (PARP) inhibitor response has not yet been studied. The present study demonstrates that PARP inhibitor (PARPi), olaparib, induces the expression and nuclear localization of FOXM1. Based on ChIP-qPCR, olaparib enhances the binding of FOXM1 to genes involved in HR repair...
March 15, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29541396/three-dimensional-organoid-culture-reveals-involvement-of-wnt-%C3%AE-catenin-pathway-in-proliferation-of-bladder-cancer-cells
#20
Takahiro Yoshida, Nikolai A Sopko, Max Kates, Xiaopu Liu, Gregory Joice, David J McConkey, Trinity J Bivalacqua
There has been increasing awareness of the importance of three-dimensional culture of cancer cells. Tumor cells growing as multicellular spheroids in three-dimensional culture, alternatively called organoids, are widely believed to more closely mimic solid tumors in situ . Previous studies concluded that the Wnt/β-catenin pathway is required for regeneration of the normal urothelium after injury and that β-catenin is upregulated in human bladder cancers, but no clear evidence has been advanced to support the idea that the Wnt/β-catenin pathway is directly involved in deregulated proliferation and the other malignant characteristics of bladder cancer cells...
February 16, 2018: Oncotarget
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