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https://www.readbyqxmd.com/read/29235495/identification-of-nonsense-mediated-mrna-decay-pathway-as-a-critical-regulator-of-p53-isoform-%C3%AE
#1
Lauren E Cowen, Yi Tang
Human TP53 gene encodes the tumor suppressor p53 and, via alternative splicing, the p53β and γ isoforms. Numerous studies have shown that p53β/γ can modulate p53 functions and are critically involved in regulation of cellular response to stress conditions. However, it is not fully understood how the β and γ isoforms are regulated following splicing. Using gene targeting and RNAi, we showed that depletion of the nonsense-mediated mRNA decay (NMD) factor SMG7 or UPF1 significantly induced p53β but had minimal effect on p53γ...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29233047/rnai-of-grp78-may-disturb-the-fusion-of-icr-mouse-palate-cultured-in-vitro
#2
C Ren, X Li, X Li, Y Xie, H Fu, Z Yan, Y Zhu
RNA interference (RNAi) is a powerful tool to silence or minimize gene expression, and palate culture in vitro is an important technique for study of the palate development. Our previous study demonstrated that the gene expression of glucose-regulated protein-78 (Grp78) was downregulation in the all-trans retinoic acid-induced mouse models of cleft palate (CP) during embryogenesis. To find the role of Grp78, the small interfering RNA (siRNA) of this gene carried by fluorescent vector was injected with a microinjector, through which about 30 pmol siRNA was injected into the Institute of Cancer Research (ICR) mouse palate explants...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29228698/osteopontin-is-involved-in-tlr4-pathway-contributing-to-ovarian-cancer-cell-proliferation-and-metastasis
#3
Cong Xu, Hua Li, Miao Yin, Tao Yang, Liguo An, Guiwen Yang
Tumor cell proliferation and metastasis are critical for tumor progression and lead to death of cancer patients. TLR4 is a member of the toll-like receptor (TLR) family, which promotes tumor growth, metastasis and immune escape. Osteopontin (OPN), a phosphorylated glycoprotein extensively expressed in multiple cell-types, plays important roles in tumorigenesis, metastasis and infiltration, and participates in signal transduction of innate immunity. However, it is unclear whether TLR4 has any relationship with OPN...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212455/comparative-gene-co-expression-network-analysis-of-epithelial-to-mesenchymal-transition-reveals-lung-cancer-progression-stages
#4
Daifeng Wang, John D Haley, Patricia Thompson
BACKGROUND: The epithelial to mesenchymal transition (EMT) plays a key role in lung cancer progression and drug resistance. The dynamics and stability of gene expression patterns as cancer cells transition from E to M at a systems level and relevance to patient outcomes are unknown. METHODS: Using comparative network and clustering analysis, we systematically analyzed time-series gene expression data from lung cancer cell lines H358 and A549 that were induced to undergo EMT...
December 6, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29212028/non-canonical-hedgehog-signaling-is-a-positive-regulator-of-the-wnt-pathway-and-is-required-for-the-survival-of-colon-cancer-stem-cells
#5
Joseph L Regan, Dirk Schumacher, Stephanie Staudte, Andreas Steffen, Johannes Haybaeck, Ulrich Keilholz, Caroline Schweiger, Nicole Golob-Schwarzl, Dominik Mumberg, David Henderson, Hans Lehrach, Christian R A Regenbrecht, Reinhold Schäfer, Martin Lange
Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH)-positive CSCs...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29210417/reactive-oxygen-species-ros-responsive-nanomedicine-for-rnai-based-cancer-therapy
#6
Yang Li, Hongzhen Bai, Hebin Wang, Youqing Shen, Guping Tang, Yuan Ping
Although much effort has been dedicated to the development of efficient siRNA delivery for cancer therapy, delivery nanomaterials that can particularly respond to reactive oxygen species (ROS), which are overproduced in the tissue and mitochondria of cancer cells, are still rare for the clinical translation of RNA interference (RNAi)-based therapy. To this end, we developed a ROS-responsive boronic vehicle with a lipid envelope for systemic vascular endothelial growth factor (VEGF) siRNA delivery so as to improve RNAi cancer therapy...
December 6, 2017: Nanoscale
https://www.readbyqxmd.com/read/29207147/effect-and-mechanism-of-rnai-targeting-wwtr1-on-biological-activity-of-gastric-cancer-cells-sgc7901
#7
Yuan Li, Fang-Liang Yang, Chun-Fu Zhu, Li-Ming Tang
Gastric cancer (GC) is one of the most common malignancies in the world. It is essential to develop novel targets and therapeutic approaches for GC, which requires identification of novel functional molecules. WW‑domain containing transcription regulator 1 (WWTR1) may activate many transcriptional factors and exhibit an important role in the development of various tissues in mammals. The results of the present study demonstrated that mRNA and protein levels of WWTR1 are increased in GC tissues and cell lines...
December 5, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29201172/construction-of-a-novel-vector-expressing-survivin-shrna-and-fusion-suicide-gene-ycdglytk-and-its-application-in-inhibiting-proliferation-and-migration-of-colon-cancer-cells
#8
Ling Ye, Yuan Yang, Xin-Yu Ma, Dan Li, Mei-Li Xu, Pan Tan, Li-Min Long, Hai-Qin Wang, Ting Liu, Yong-Hong Guo
Despite progress achieved in cancer chemotherapy in recent decades, adverse effects remain a limiting factor for a number of patients with colorectal cancer, suggesting the requirement for novel therapeutic strategies. Gene therapy appears to be a promising strategy for treating cancer. The present study aimed to investigate the anti-tumor effect of a combined gene therapy, using Survivin downregulation by RNAi and a fusion suicide gene yCDglyTK therapy system. A triple-gene vector expressing Survivin-targeted small hairpin RNA (Survivin-shRNA) and fusion suicide gene yCDglyTK was constructed, and administered to HCT116 cells...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29191012/tape-assisted-photolithographic-free-microfluidic-chip-tapmic-cell-patterning-for-tumor-metastasis-study
#9
Liang Zhao, Tengfei Guo, Lirong Wang, Yang Liu, Ganyu Chen, Hao Zhou, Meiqin Zhang
Cancer metastatic dissemination is a complex event during tumor progression which involves cell-cell, cell-matrix interactions. Micro-patterning of is one of the most efficient ways to study tumor development because it can tune the distribution of cells with spatial and temporal control. Extensive studies have shown that microfluidics can provide a feasible method for cell patterning. However, the current technique requires a microfabrication laboratory to manufacture the chip, which results in inaccessibility to researchers especially biologists who focus on the disclosing biological mechanisms rather than the methods...
November 30, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29182622/cisplatin-or-la-12-enhance-killing-effects-of-trail-in-prostate-cancer-cells-through-bid-dependent-stimulation-of-mitochondrial-apoptotic-pathway-but-not-caspase-10
#10
Olga Vondálová Blanářová, Barbora Šafaříková, Jarmila Herůdková, Martin Krkoška, Silvie Tománková, Zuzana Kahounová, Ladislav Anděra, Jan Bouchal, Gvantsa Kharaishvili, Milan Král, Petr Sova, Alois Kozubík, Alena Hyršlová Vaculová
Searching for new strategies for effective elimination of human prostate cancer cells, we investigated the cooperative cytotoxic action of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and two platinum-based complexes, cisplatin or LA-12, and related molecular mechanisms. We demonstrated a notable ability of cisplatin or LA-12 to enhance the sensitivity of several human prostate cancer cell lines to TRAIL-induced cell death via an engagement of mitochondrial apoptotic pathway. This was accompanied by augmented Bid cleavage, Bak activation, loss of mitochondrial membrane potential, activation of caspase-8, -10, -9, and -3, and XIAP cleavage...
2017: PloS One
https://www.readbyqxmd.com/read/29179464/urokinase-type-plasminogen-activator-receptor-inhibits-apoptosis-in-triple-negative-breast-cancer-through-mir-17-20a-suppression-of-death-receptors-4-and-5
#11
Xin Li, Bo Wu, Lizhao Chen, Ying Ju, Changfei Li, Songdong Meng
Dissection and understanding of the molecular pathways driving triple-negative breast cancer (TNBC) are urgently needed to develop efficient tailored therapies. Aside from cell invasion and metastasis, the urokinase-type plasminogen activator receptor (uPAR) has been linked to apoptosis resistance in breast tumors. We explored the mechanism of uPAR-disrupted apoptosis in breast cancer. We found that depletion of uPAR by RNAi increases death receptor 4 (DR4) and death receptor 5 (DR5) expression and triggers TRAIL-induced apoptosis in TNBC cells...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29179130/predictive-bioinformatics-identifies-novel-regulators-of-proliferation-in-a-cancer-stem-cell-model
#12
Evan Fields, Jonathan D Wren, Constantin Georgescu, John R Daum, Gary J Gorbsky
The cancer stem cell model postulates that tumors are hierarchically organized with a minor population, the cancer stem cells, exhibiting unlimited proliferative potential. These cells give rise to the bulk of tumor cells, which retain a limited ability to divide. Without successful targeting of cancer stem cells, tumor reemergence after therapy is likely. However, identifying target pathways essential for cancer stem cell proliferation has been challenging. Here, using a transcriptional network analysis termed GAMMA, we identified 50 genes whose correlation patterns suggested involvement in cancer stem cell division...
November 21, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29169420/-knockdown-of-akt1-gene-enhances-the-sensitivity-of-gastric-cancer-xenografts-of-nude-mice-to-doxorubicin
#13
Wei Zhou, Xueqiong Fu, Honggang Yu
Objective To investigate the effect of lentivirus-mediated shRNA targeting AKT1 gene on the sensitivity of gastric cancer xenografts to doxorubicin. Methods To establish the lentiviral vector of AKT1 RNA interference (RNAi), the vector of pGCSIL-shAKT1-GFP was infected into HEK293T cells, and meanwhile, the empty vector pGCSIL-shCON-GFP was assigned as a blank group, and then the viruses were harvested. BGC-823 gastric cancer cells were infected with the viruses. The protein expression of AKT1 was detected by Western blotting...
October 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/29167765/role-of-molecular-biology-in-cancer-treatment-a-review-article
#14
REVIEW
Aman Imran, Hafiza Yasara Qamar, Qurban Ali, Hafsa Naeem, Mariam Riaz, Saima Amin, Naila Kanwal, Fawad Ali, Muhammad Farooq Sabar, Idrees Ahmad Nasir
Background: Cancer is a genetic disease and mainly arises due to a number of reasons include activation of onco-genes, malfunction of tumor suppressor genes or mutagenesis due to external factors. Methods: This article was written from the data collected from PubMed, Nature, Science Direct, Springer and Elsevier groups of journals. Results: Oncogenes are deregulated form of normal proto-oncogenes required for cell division, differentiation and regulation...
November 2017: Iranian Journal of Public Health
https://www.readbyqxmd.com/read/29164017/the-daniel-k-inouye-college-of-pharmacy-scripts-targeted-nanocarrier-based-systems-for-the-treatment-of-lung-cancer
#15
Susanne R Youngren-Ortiz, Mahavir B Chougule
In Hawai'i, lung cancer is among the top cancers diagnosed and a leading cause of death. Despite current understanding and modern surgery, radiology, and chemotherapy techniques, the survival of those suffering from lung cancer remains low. Current anticancer drugs have poor tumor tissue selectivity and toxicity issues that contribute to their overall low efficacy, detrimental effects to normal tissues, and drug resistance. A potential way of mitigating cancer is through RNA interference (RNAi) by the delivery of small interfering RNA (siRNA) to target select proteins or genes involved in cancer progression, known as oncoproteins or oncogenes, respectively...
November 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/29163813/the-novel-zip4-regulation-and-its-role-in-ovarian-cancer
#16
Qipeng Fan, Qingchun Cai, Pengfei Li, Wenyan Wang, Jing Wang, Emily Gerry, Tian-Li Wang, Ie-Ming Shih, Kenneth P Nephew, Yan Xu
Our RNAseq analyses revealed that ZIP4 is a top gene up-regulated in more aggressive ovarian cancer cells. ZIP4's role in cancer stem cells has not been reported in any type of cancer. In addition, the role and regulation of ZIP4, a zinc transporter, have been studied in the context of extracellular zinc transporting. Factors other than zinc with ZIP4 regulatory effects are essentially unknown. ZIP4 expression and its regulation in epithelial ovarian cancer cells was assessed by immunoblotting, quantitative PCR, or immunohistochemistry staining in human ovarian tissues...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29158600/crispr-cas9-library-screening-for-drug-target-discovery
#17
REVIEW
Morito Kurata, Kouhei Yamamoto, Branden S Moriarity, Masanobu Kitagawa, David A Largaespada
CRISPR/Cas9-based tools have rapidly developed in recent years. These include CRISPR-based gene activation (CRISPRa) or inhibition (CRISPRi), for which there are libraries. CRISPR libraries for loss of function have been widely used to identify new biological mechanisms, such as drug resistance and cell survival signals. CRISPRa is highly useful in screening for gain of functions, and CRISPRi is a more powerful tool than RNA interference (RNAi) libraries in screening for loss of functions. Positive selection using a CRISPR library can detect survival cells with specific conditions, such as drug treatment, and it can easily clarify drug resistance mechanisms...
November 20, 2017: Journal of Human Genetics
https://www.readbyqxmd.com/read/29158292/sphingomyelin-metabolism-is-a-regulator-of-kras-function
#18
Dharini van der Hoeven, Kwang-Jin Cho, Yong Zhou, Xiaoping Ma, Wei Chen, Ali Naji, Dina Montufar-Solis, Yan Zuo, Sarah E Kovar, Kandice R Levental, Jeffrey A Frost, Ransome van der Hoeven, John F Hancock
KRAS must localize to the plasma membrane (PM) for biological activity. We show here that multiple acid sphingomyelinase (ASM) inhibitors, including tricyclic antidepressants, mislocalized phosphatidylserine (PtdSer) and KRASG12V from the PM; resulting in abrogation of KRASG12V signaling and potent, selective growth inhibition of mutant KRAS transformed cancer cells. Concordantly, in nude mice, the ASM inhibitor fendiline decreased the rate of growth of oncogenic KRAS-expressing MiaPaCa-2 tumors, but had no effect on the growth of the wild-type KRAS-expressing BxPC-3 tumors...
November 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29156673/induction-of-dise-in-ovarian-cancer-cells-in-vivo
#19
Andrea E Murmann, Kaylin M McMahon, Ashley Haluck-Kangas, Nandini Ravindran, Monal Patel, Calvin Y Law, Sonia Brockway, Jian-Jun Wei, C Shad Thaxton, Marcus E Peter
The death receptor CD95/Fas can be activated by immune cells to kill cancer cells. shRNAs and siRNAs derived from CD95 or CD95 ligand (CD95L) are highly toxic to most cancer cells. We recently found that these sh/siRNAs kill cancer cells in the absence of the target by targeting the 3'UTRs of critical survival genes through canonical RNAi. We have named this unique form of off-target effect DISE (for death induced by survival gene elimination). DISE preferentially kills transformed cells and cancer stem cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29150005/crispr-libraries-and-screening
#20
John T Poirier
CRISPR-Cas9 technology has revolutionized large-scale functional genomic screening in mammalian cell-culture systems. Due in part to optimized lentiviral delivery vectors; it is now possible to perform CRISPR-Cas9 screens in animals in order to study biological processes in the context of a whole organism and within more physiologically relevant environment. This chapter focuses primarily on mouse models of human cancers; viral vectors used for simultaneous tumor initiation and genome editing and sgRNA library design considerations...
2017: Progress in Molecular Biology and Translational Science
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