keyword
https://read.qxmd.com/read/38104314/gene-regulatory-network-analysis-predicts-cooperating-transcription-factor-regulons-required-for-flt3-itd-aml-growth
#21
JOURNAL ARTICLE
Daniel J L Coleman, Peter Keane, Rosario Luque-Martin, Paulynn S Chin, Helen Blair, Luke Ames, Sophie G Kellaway, James Griffin, Elizabeth Holmes, Sandeep Potluri, Salam A Assi, John Bushweller, Olaf Heidenreich, Peter N Cockerill, Constanze Bonifer
Acute myeloid leukemia (AML) is a heterogeneous disease caused by different mutations. Previously, we showed that each mutational subtype develops its specific gene regulatory network (GRN) with transcription factors interacting within multiple gene modules, many of which are transcription factor genes themselves. Here, we hypothesize that highly connected nodes within such networks comprise crucial regulators of AML maintenance. We test this hypothesis using FLT3-ITD-mutated AML as a model and conduct an shRNA drop-out screen informed by this analysis...
December 15, 2023: Cell Reports
https://read.qxmd.com/read/38064851/machine-learning-based-classification-of-deubiquitinase-usp26-and-its-cell-proliferation-inhibition-through-stabilizing-klf6-in-cervical-cancer
#22
JOURNAL ARTICLE
Ying Ye, Meng Li, Qilong Pan, Xin Fang, Hong Yang, Bingying Dong, Jiaying Yang, Yuan Zheng, Renxiang Zhang, Zhijun Liao
OBJECTIVE: We aim to accurately distinguish ubiquitin-specific proteases (USPs) from other members within the deubiquitinating enzyme families based on protein sequences. Additionally, we seek to elucidate the specific regulatory mechanisms through which USP26 modulates Krüppel-like factor 6 (KLF6) and assess the subsequent effects of this regulation on both the proliferation and migration of cervical cancer cells. METHODS: All the deubiquitinase (DUB) sequences were classified into USPs and non-USPs...
November 28, 2023: Computers in Biology and Medicine
https://read.qxmd.com/read/38050666/guanylate-binding-protein-5-mediated-cell-autonomous-immunity-suppresses-inflammation-in-dental-pulpitis-an%C3%A2-in%C3%A2-vitro-study
#23
JOURNAL ARTICLE
Minchun Huang, Chaoning Zhan, Bo Yang, Yanli Lu, Xiaojun Yang, Jin Hou
AIM: Guanylate-binding protein 5 (GBP5) is an interferon (IFN)-inducible GTPase that plays a crucial role in the cell-autonomous immune response against microbial infections. In this study, we investigated the immunoregulatory role of GBP5 in the pathogenesis of dental pulpitis. METHODOLOGY: Gene-set enrichment analysis (GSEA) was utilized to evaluate the IFN-γ signalling pathway, and the differential expression of GBP mRNA in normal versus inflamed dental pulp tissues was screened, based on Gene Expression Omnibus (GEO) datasets associated with pulpitis...
December 5, 2023: International Endodontic Journal
https://read.qxmd.com/read/38035705/circular-rna-in-non-small-cell-lung-carcinoma-identification-of-targets-and-new-treatment-modalities
#24
REVIEW
Ulrich H Weidle, Fabian Birzele
Despite availability of several treatment options for non-small cell lung cancer (NSCLC), such as surgery, chemotherapy, radiation, targeted therapy and immunotherapy, the survival rate of patients for five years is in the range of 22%. Therefore, identification of new targets and treatment modalities for this disease is an important issue. In this context, we screened the PubMed database for up-regulated circular RNAs (circRNAs) which promote growth of NSCLC in preclinical models in vitro as well as in vivo xenograft models in immuno-compromised mice...
December 2023: Cancer Genomics & Proteomics
https://read.qxmd.com/read/38014177/ifih1-mda5-is-required-for-innate-immune-detection-of-intron-containing-rna-expressed-from-the-hiv-1-provirus
#25
Mehmet Hakan Guney, Karthika Nagalekshmi, Sean Matthew McCauley, Claudia Carbone, Ozkan Aydemir, Jeremy Luban
Antiretroviral therapy (ART) suppresses HIV-1 viremia and prevents progression to AIDS. Nonetheless, chronic inflammation is a common problem for people living with HIV-1 on ART. One possible cause of inflammation is ongoing transcription from HIV-1 proviruses, whether or not the sequences are competent for replication. Previous work has shown that intron-containing RNA expressed from the HIV-1 provirus in primary human blood cells, including CD4+ T cells, macrophages, and dendritic cells, activates type 1 interferon...
November 18, 2023: bioRxiv
https://read.qxmd.com/read/38014168/suppressing-dnmt3a-alleviates-the-intrinsic-epigenetic-barrier-for-optic-nerve-regeneration-and-restores-vision-in-adult-mice
#26
Wai Lydia Tai, Kin-Sang Cho, Emil Kriukov, Ajay Ashok, Xuejian Wang, Aboozar Monavarfeshani, Wenjun Yan, Yingqian Li, Timothy Guan, Joshua R Sanes, Petr Baranov, Dong Feng Chen
The limited regenerative potential of the optic nerve in adult mammals presents a major challenge for restoring vision after optic nerve trauma or disease. The mechanisms of this regenerative failure are not fully understood 1,2 . Here, through small-molecule and genetic screening for epigenetic modulators 3 , we identify DNA methyltransferase 3a (DNMT3a) as a potent inhibitor of axon regeneration in mouse and human retinal explants. Selective suppression of DNMT3a in retinal ganglion cells (RGCs) by gene targeting or delivery of shRNA leads to robust, full-length regeneration of RGC axons through the optic nerve and restoration of vision in adult mice after nerve crush injury...
November 23, 2023: bioRxiv
https://read.qxmd.com/read/38011799/chaetocin-mediated-suv39h1-inhibition-targets-stemness-and-oncogenic-networks-of-diffuse-midline-gliomas-and-synergizes-with-onc201
#27
JOURNAL ARTICLE
Dazhuan Eric Xin, Yunfei Liao, Rohit Rao, Sean Ogurek, Soma Sengupta, Mei Xin, William L Seibel, Richard T Graham, Carl Koschmann, Q Richard Lu
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPG/DMG) are devastating pediatric brain tumors with extraordinarily limited treatment options and uniformly fatal prognosis. Histone H3K27M mutation is a common recurrent alteration in DIPG and disrupts epigenetic regulation. We hypothesize that genome-wide H3K27M-induced epigenetic dysregulation makes tumors vulnerable to epigenetic targeting. METHODS: We performed a screen of compounds targeting epigenetic enzymes to identify potential inhibitors for the growth of patient-derived DIPG cells...
November 27, 2023: Neuro-oncology
https://read.qxmd.com/read/37983968/a-new-strategy-for-screening-novel-functional-genes-involved-in-reduction-of-lipid-droplet-accumulation
#28
JOURNAL ARTICLE
Ryuto Maruyama, Yasuhiro Kudo, Tomoyasu Sugiyama
Lipid droplets (LDs) are organelles that store excess lipids and provide fatty acids for energy production during starvation. LDs are also essential for cellular maintenance, but excessive accumulation of LDs triggers various cancers in addition to metabolic diseases such as diabetes. In this study, we aimed to develop a strategy to identify new genes that reduces accumulation of LDs in cancer cells using an RNA interference (RNAi) screening system employing artificial sequence-enriched shRNA libraries. Monitoring LDs by fluorescent activated cell sorting, the subsequently collected cumulative LDs cells, and shRNA sequence analysis identified a clone that potentially functioned to accumulate LDs...
November 20, 2023: BioFactors
https://read.qxmd.com/read/37882787/high-content-screening-of-synaptic-density-modulators-in-primary-neuronal-cultures
#29
JOURNAL ARTICLE
Audrey Coulon, Dolores Siedlecki-Wullich, Chloé Najdek, Carla Gelle, Anne-Marie Ayral, Florie Demiautte, Erwan Lambert, Alexandre Vandeputte, Priscille Brodin, Tiago Mendes, Jean-Charles Lambert, Devrim Kilinc, Julie Dumont, Julien Chapuis
The synapse, which represents the structural and functional basis of neuronal communication, is one of the first elements affected in several neurodegenerative diseases. To better understand the potential role of gene expression in synapse loss, we developed an original high-content screening (HCS) model capable of quantitatively assessing the impact of gene silencing on synaptic density. Our approach is based on a model of primary neuronal cultures (PNCs) from the neonatal rat hippocampus, whose mature synapses are visualized by the relative localization of the presynaptic protein Synaptophysin with the postsynaptic protein Homer1...
October 2023: Current protocols
https://read.qxmd.com/read/37873383/functional-genomics-reveals-that-a-divergent-genetic-dependency-signature-is-not-essential-to-the-synergism-of-molecular-targeted-agent-and-chemotherapeutic-combinations-in-gastric-cancer-cells
#30
Ozen Leylek, Megan E Honeywell, Michael J Lee, Michael T Hemann, Gulnihal Ozcan
UNLABELLED: The rational combination of anticancer agents is critical to improving patient outcomes in cancer. Nonetheless, most combination regimens in the clinic result from empirical methodologies disregarding insight into the mechanism of action and missing the opportunity to improve therapy outcomes incrementally. Deciphering the genetic dependencies and vulnerabilities responsible for synergistic interactions is crucial for rationally developing effective anticancer drug combinations...
October 10, 2023: bioRxiv
https://read.qxmd.com/read/37863651/pathway-driven-analysis-of-synthetic-lethal-interactions-in-cancer-using-perturbation-screens
#31
JOURNAL ARTICLE
Mina Karimpour, Mehdi Totonchi, Mehrdad Behmanesh, Hesam Montazeri
Synthetic lethality offers a promising approach for developing effective therapeutic interventions in cancer when direct targeting of driver genes is impractical. In this study, we comprehensively analyzed large-scale CRISPR, shRNA, and PRISM screens to identify potential synthetic lethal (SL) interactions in pan-cancer and 12 individual cancer types, using a new computational framework that leverages the biological function and signaling pathway information of key driver genes to mitigate the confounding effects of background genetic alterations in different cancer cell lines...
January 2024: Life Science Alliance
https://read.qxmd.com/read/37852393/dnajs-are-enriched-in-tau-regulators
#32
JOURNAL ARTICLE
Abigail R Esquivel, Shannon E Hill, Laura J Blair
The aberrant accumulation of tau protein is implicated as a pathogenic factor in many neurodegenerative diseases. Tau seeding may underlie its predictable spread in these diseases. Molecular chaperones can modulate tau pathology, but their effects have mainly been studied in isolation. This study employed a semi-high throughput assay to identify molecular chaperones influencing tau seeding using Tau RD P301S FRET Biosensor cells, which express a portion of tau containing the frontotemporal dementia-related P301S tau mutation fused to a FRET biosensor...
October 16, 2023: International Journal of Biological Macromolecules
https://read.qxmd.com/read/37819945/fak-drives-resistance-to-therapy-in-hpv-negative-head-and-neck-cancer-in-a-p53-dependent-manner
#33
JOURNAL ARTICLE
Phillip M Pifer, Liangpeng Yang, Manish Kumar, Tongxin Xie, Mitchell Frederick, Andrew Hefner, Beth Beadle, David Molkentine, Jessica Molkentine, Annika Dhawan, Mohamed Abdelhakiem, Abdullah A Osman, Brian J Leibowitz, Jeffrey N Myers, Curtis R Pickering, Vlad C Sandulache, John Heymach, Heath D Skinner
PURPOSE: Radiation and platinum-based chemotherapy form the backbone of therapy in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). We have correlated focal adhesion kinase (FAK/PTK2) expression with radioresistance and worse outcomes in these patients. However, the importance of FAK in driving radioresistance and its effects on chemoresistance in these patients remains unclear. EXPERIMENTAL DESIGN: We performed an in vivo shRNA screen using targetable libraries to identify novel therapeutic sensitizers for radiation and chemotherapy...
January 5, 2024: Clinical Cancer Research
https://read.qxmd.com/read/37805442/-effect-of-slc7a11-gene-downregulation-on-the-gefitinib-resistance-of-lung-adenocarcinoma-pc9-gr-cells-and-its-mechanism
#34
JOURNAL ARTICLE
Y L Jia, Y Zhao, S M Zhen, Z S Cheng, B Y Zheng, Y P Liu, L H Liu
Objective: To screen the key genes involved in gefitinib resistance of lung adenocarcinoma PC9/GR cells which harbored 19 exon mutation of epidermal growth factor receptor (EGFR) gene, and discuss the effect and mechanism of downregulation of solute carrier family 7 member 11 (SLC7A11) on the gefitinib resistance of PC9/GR cells. Methods: RNA microarray was conducted to detect the gene expressions in PC9 and PC9/GR cells. The differently expressed genes were screened by using limma package of R language and analyzed by Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis...
September 23, 2023: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://read.qxmd.com/read/37804922/inhibition-of-apoc1-reverses-resistance-of-sorafenib-by-promoting-ferroptosis-in-esophageal-cancers
#35
JOURNAL ARTICLE
Jie Hu, Hai Hu, Qilong Liu, Bi Feng, Yanling Lu, Kai Chen
Drug resistance is an obstacle in therapy of esophageal cancers (ECs), and the role of ferroptosis in progression ECs is still not clearly clarified. In the present study, we investigated the role of Apolipoprotein C1 (Apoc1) in regulating the sorafenib resistance in EC cells. Apoc1 was knock down after infection with Apoc1 shRNA lentivirus and stable cell lines for Apoc1 knockdown were screened. Cell viabilities were tested by MTT assay. ROS, MDA, and GSH tested by specific kits. In vivo experiment in nude mice were performed to test the correlation of Apoc1 and ferroptosis...
October 5, 2023: Gene
https://read.qxmd.com/read/37793878/direct-screening-for-effective-shrna-with-a-single-mismatch-in-human-cells-without-laborious-cloning
#36
JOURNAL ARTICLE
Mayu Tachibana, Nazumi Ehara, Shunya Tanikawa, Akira Tachibana
We have devised a method for the direct screening of efficient short hairpin (sh)RNA molecules in human cells, eliminating the need for the time-consuming process of cloning in Escherichia coli. Our screening suggested that single mismatches to shRNAs can significantly alter their activity.
October 4, 2023: Bioscience, Biotechnology, and Biochemistry
https://read.qxmd.com/read/37773632/hyper-dependence-on-nhej-enables-synergy-between-dna-pk-inhibitors-and-low-dose-doxorubicin-in-leiomyosarcoma
#37
JOURNAL ARTICLE
Adrián Mariño-Enríquez, Jan Philipp Novotny, Doga C Gulhan, Isabella Klooster, Antuan V Tran, Macy Kasbo, Meijun Z Lundberg, Wen-Bin Ou, Derrick L Tao, Daniel F Pilco-Janeta, Victor Y Mao, Frank T Zenke, Brittaney A Leeper, Prafulla C Gokhale, Glenn S Cowley, Laurence H Baker, Karla V Ballman, David E Root, Joachim Albers, Peter J Park, Suzanne George, Jonathan A Fletcher
PURPOSE: Leiomyosarcoma (LMS) is an aggressive sarcoma for which standard chemotherapies achieve response rates under 30%. There are no effective targeted therapies against LMS. Most LMS are characterized by chromosomal instability (CIN), resulting in part from TP53 and RB1 co-inactivation and DNA damage repair defects. We sought to identify therapeutic targets that could exacerbate intrinsic CIN and DNA damage in LMS, inducing lethal genotoxicity. EXPERIMENTAL DESIGN: We performed clinical targeted sequencing in 287 LMS and genome-wide loss-of-function screens in 3 patient-derived LMS cell lines, to identify LMS-specific dependencies...
September 29, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37729426/genome-wide-crispr-screens-identify-multiple-synthetic-lethal-targets-that-enhance-krasg12c-inhibitor-efficacy
#38
JOURNAL ARTICLE
Suman Mukhopadhyay, Hsin-Yi Huang, Ziyan Lin, Michela Ranieri, Shuai Li, Soumyadip Sahu, Yingzhuo Liu, Yi Ban, Kayla Guidry, Hai Hu, Alfonso Lopez, Fiona Sherman, Yi Jer Tan, Yeuan Ting Lee, Amanda P Armstrong, Igor Dolgalev, Priyanka Sahu, Tinghu Zhang, Wenchao Lu, Nathanael S Gray, James G Christensen, Tracy T Tang, Vamsidhar Velcheti, Alireza Khodadadi-Jamayran, Kwok-Kin Wong, Benjamin G Neel
UNLABELLED: Non-small lung cancers (NSCLC) frequently (∼30%) harbor KRAS driver mutations, half of which are KRASG12C. KRAS-mutant NSCLC with comutated STK11 and/or KEAP1 is particularly refractory to conventional, targeted, and immune therapy. Development of KRASG12C inhibitors (G12Ci) provided a major therapeutic advance, but resistance still limits their efficacy. To identify genes whose deletion augments efficacy of the G12Cis adagrasib (MRTX-849) or adagrasib plus TNO155 (SHP2i), we performed genome-wide CRISPR/Cas9 screens on KRAS/STK11-mutant NSCLC lines...
December 15, 2023: Cancer Research
https://read.qxmd.com/read/37717172/crispr-screen-identifies-cebpb-as-contributor-to-dyskeratosis-congenita-fibroblast-senescence-via-augmented-inflammatory-gene-response
#39
JOURNAL ARTICLE
Erik R Westin, Alireza Khodadadi-Jamayran, Linh K Pham, Moon Ley Tung, Frederick D Goldman
Aging is the consequence of intra- and extracellular events that promote cellular senescence. Dyskeratosis congenita (DC) is an example of a premature aging disorder caused by underlying telomere/telomerase-related mutations. Cells from these patients offer an opportunity to study telomere-related aging and senescence. Our previous work has found that telomere shortening stimulates DNA damage responses (DDR) and increases reactive oxygen species (ROS), thereby promoting entry into senescence. This work also found that telomere elongation via TERT expression, the catalytic component of the telomere-elongating enzyme telomerase, or p53 shRNA could decrease ROS by disrupting this telomere-DDR-ROS pathway...
September 17, 2023: G3: Genes—Genomes—Genetics
https://read.qxmd.com/read/37716420/multi-omics-profiling-reveals-cellular-pathways-and-functions-regulated-by-aldh1b1-in-colon-cancer-cells
#40
JOURNAL ARTICLE
Yewei Wang, Zeljka Popovic, Georgia Charkoftaki, Rolando Garcia-Milian, TuKiet T Lam, David C Thompson, Ying Chen, Vasilis Vasiliou
Colon cancer is the third leading cause of cancer death globally. Although early screenings and advances in treatments have reduced mortality since 1970, identification of novel targets for therapeutic intervention is needed to address tumor heterogeneity and recurrence. Previous work identified aldehyde dehydrogenase 1B1 (ALDH1B1) as a critical factor in colon tumorigenesis. To investigate further, we utilized a human colon adenocarcinoma cell line (SW480) in which the ALDH1B1 protein expression has been knocked down by 80% via shRNA...
September 14, 2023: Chemico-biological Interactions
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