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https://www.readbyqxmd.com/read/29050242/mir-34a-modulates-ionizing-radiation-induced-senescence-in-lung-cancer-cells
#1
Xiaoyuan He, Aimin Yang, Daniel G McDonald, Ellen C Riemer, Kenneth N Vanek, Bradley A Schulte, Gavin Y Wang
MicroRNAs (miRNAs) are a new class of gene expression regulators that have been implicated in tumorigenesis and modulation of the responses to cancer treatment including that of human non-small cell lung cancer (NSCLC). However, the role of miR-34a in ionizing radiation (IR)-induced senescence in NSCLC cells remains poorly understood. Here we report that IR-induced premature senescence correlates with upregulation of miR-34a expression in NSCLC cells. Ectopic overexpression of miR-34a by transfection with synthetic miR-34a mimics markedly enhances IR-induced senescence, whereas inhibition of miR-34a by transfection with a synthetic miR-34a inhibitor attenuates IR-induced senescence...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29048618/dual-action-of-nsc606985-on-cell-growth-and-apoptosis-mediated-through-pkc%C3%AE-in-prostatic-cancer-cells
#2
Xin Wang, Chen Tan, Guo Wang, Jing-Jing Cai, Li-Ping Wang, Julianne Imperato-McGinley, Yuan-Shan Zhu
Chemotherapy is a vital therapeutic strategy for castration-resistant prostate cancer (CRPC). We have previously shown that NSC606985 (NSC), a camptothecin (CPT) analog, induced cell apoptosis via interacting with topoisomerase I (Topo I) in prostate cancer cells. In the present study, the effect and mechanism of CPT analogs in LAPC4 cells were investigated. LAPC-4 cells were treated with NSC, CPT, and topotecan. Cell proliferation, apoptosis, and protein kinase Cδ (PKCδ) subcellular activation were measured at different doses and time-points, with or without PKCδ inhibition or knockdown of PKCδ expression...
September 27, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29042969/silencing-of-tctn1-inhibits-proliferation-induces-cell-cycle-arrest-and-apoptosis-in-human-thyroid-cancer
#3
Peipei Xu, Xiaotian Xia, Zhili Yang, Yuan Tian, Jianzhong Di, Minggao Guo
Tectonic family member 1 (TCTN1) is one of the tectonic family members, and a regulator of the hedgehog signaling pathway, which has been studied in various cancer types, including prostate and pancreatic cancer. However, its function in thyroid cancer has not been well documented. Therefore, the present study investigated the function of TCTN1 in thyroid cancer using a loss-of-function assay. Lentivirus-mediated RNA interference was applied to downregulate TCTN1 in the thyroid cancer cell lines, CAL62 and 8305C...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29031805/aptamer-targeted-delivery-of-bcl-xl-shrna-using-alkyl-modified-pamam-dendrimers-into-lung-cancer-cells
#4
Sara Ayatollahi, Zahra Salmasi, Maryam Hashemi, Saeedeh Askarian, Reza Kazemi Oskuee, Khalil Abnous, Mohammad Ramezani
RNAi-based gene therapy has been recently considered as a promising approach against cancer. Targeted delivery of drug, gene or therapeutic RNAi-based systems to tumor cells is one of the important issues in order to reduce side effects on normal cells. Several strategies have been developed to improve the safety and selectivity of cancer treatments including antibodies, peptides and recently aptamers with various attractive characteristics including higher target specificity, affinity and reduced toxicity...
October 11, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29026529/coordinating-erk-signaling-via-the-molecular-scaffold-kinase-suppressor-of-ras
#5
REVIEW
Danielle Frodyma, Beth Neilsen, Diane Costanzo-Garvey, Kurt Fisher, Robert Lewis
Many cancers, including those of the colon, lung, and pancreas, depend upon the signaling pathways induced by mutated and constitutively active Ras. The molecular scaffolds Kinase Suppressor of Ras 1 and 2 (KSR1 and KSR2) play potent roles in promoting Ras-mediated signaling through the Raf/MEK/ERK kinase cascade. Here we summarize the canonical role of KSR in cells, including its central role as a scaffold protein for the Raf/MEK/ERK kinase cascade, its regulation of various cellular pathways mediated through different binding partners, and the phenotypic consequences of KSR1 or KSR2 genetic inactivation...
2017: F1000Research
https://www.readbyqxmd.com/read/29026318/rnai-mediated-knockdown-of-caix-enhances-the-radiosensitivity-of-nasopharyngeal-carcinoma-cell-line-cne-2
#6
Liji Jiang, Gang Xu, Zihuang Li, Xiaowei Zeng, Zhuangling Li, Jingwen Liu, Lin Mei, Xianming Li
Although radiotherapy remains the most powerful as well as the primary treatment modality for nasopharyngeal carcinoma (NPC), approximately 20% of NPC patients still have local recurrence. Carbonic anhydrase IX (CAIX)-related signaling pathways that mediate radioresistance have been found in various kinds of cancer. However, the role of CAIX in NPC radioresistance is still unknown. In this study, we investigated the effect of CAIX silencing on sensitization to ionizing radiation in NPC by using Lipofectamine 2000, which delivers small interfering ribonucleic acid (siRNA) that targets CAIX...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29026202/loss-of-abhd5-promotes-the-aggressiveness-of-prostate-cancer-cells
#7
Guohua Chen, Guoli Zhou, Siddhesh Aras, Zhenhui He, Stephanie Lucas, Izabela Podgorski, Wael Skar, James G Granneman, Jian Wang
The accumulation of neutral lipids in intracellular lipid droplets has been associated with the formation and progression of many cancers, including prostate cancer (PCa). Alpha-beta Hydrolase Domain Containing 5 (ABHD5) is a key regulator of intracellular neutral lipids that has been recently identified as a tumor suppressor in colorectal cancer, yet its potential role in PCa has not been investigated. Through mining publicly accessible PCa gene expression datasets, we found that ABHD5 gene expression is markedly decreased in metastatic castration-resistant PCa (mCRPC) samples...
October 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28993509/a-large-scale-rnai-screen-identifies-sgk1-as-a-key-survival-kinase-for-gbm-stem-cells
#8
Shreya Kulkarni, Surbhi Goel, Sejuti Sengupta, Brent H Cochran
Glioblastoma Multiforme (GBM) is the most common type of primary malignant brain cancer and has a very poor prognosis. A subpopulation of cells known as GBM stem-like cells (GBM-SCs) have the capacity to initiate and sustain tumor growth and possess molecular characteristics similar to the parental tumor. GBM-SCs are known to be enriched in hypoxic niches and may contribute to therapeutic resistance. Therefore, to identify genetic determinants important for the proliferation and survival of GBM stem cells, an unbiased pooled shRNA screen of 10,000 genes was conducted under normoxic as well as hypoxic conditions...
October 9, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28989537/effect-of-inhibiting-beclin-1-expression-on-autophagy-proliferation-and-apoptosis-in-colorectal-cancer
#9
Lin Liu, Wei-Min Zhao, Xin-Hui Yang, Zhen-Qiang Sun, Hui-Zhen Jin, Cheng Lei, Bo Jin, Hai-Jiang Wang
The present study aimed to investigate the molecular mechanisms and effect of Beclin-1 on autophagy, proliferation and apoptosis in the colorectal cancer (CRC) HCT116 and SW620 cells. Beclin-1 was silenced by RNA interference (RNAi) in HTC116 and SW620 cells. Reverse transcription-polymerase chain reaction and western blot were used to measure the expression of Beclin-1. The percentage of apoptotic cells was analyzed by cell counting kit-8 (CCK-8) and flow cytometry (FCM). Cell cycle and cell proliferation were analyzed by FCM and the MTT assay...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28981102/regulation-of-rip3-by-the-transcription-factor-sp1-and-the-epigenetic-regulator-uhrf1-modulates-cancer-cell-necroptosis
#10
Chengkui Yang, Jun Li, Lu Yu, Zili Zhang, Feng Xu, Lang Jiang, Xiuxia Zhou, Sudan He
Receptor-interacting kinase-3 (RIP3) is a key regulator of necroptosis. It has been shown that the expression of RIP3 is silenced in most cancer cells and tissues due to genomic methylation. However, the regulatory mechanisms controlling RIP3 expression in cancer cells have not been fully elucidated. Here, we report that Sp1, a well-characterized zinc-finger transcription factor, directly regulates RIP3 expression in cancer cells. Knockdown of endogenous Sp1 significantly decreases the transcription of Rip3, thereby further inhibiting necroptosis...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28979669/comprehensive-analysis-of-long-non-coding-rna-pvt1-gene-interaction-regulatory-network-in-hepatocellular-carcinoma-using-gene-microarray-and-bioinformatics
#11
Yu Zhang, Yi-Wu Dang, Xiao Wang, Xia Yang, Rui Zhang, Zi-Li Lv, Gang Chen
PVT1 has been reported to be involved in the tumorigenesis and development of different cancers. However, the role of PVT1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we applied gene microarray analysis to detect differentially expressed genes (DEGs) between PVT1 RNAi groups and controls. We initially investigated and confirmed PVT1 expression in HCC using The Cancer Genome Atlas (TCGA). The potential genes and pathways associated with PVT1 were also analyzed. We also performed bioinformatics analyses (Gene Ontology (GO), pathway, Kyoto Encyclopedia of Genes and Genomes (KEGG), and network analyses) to explore the underlying pathways and networks of these potential genes...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28972570/high-throughput-rnai-screen-for-essential-genes-and-drug-synergistic-combinations-in-colorectal-cancer
#12
Steven P Williams, Andrew S Barthorpe, Howard Lightfoot, Mathew J Garnett, Ultan McDermott
Metastatic colorectal cancer is a leading cause of cancer death. However, current therapy options are limited to chemotherapy, with the addition of anti-EGFR antibodies for patients with RAS wild-type tumours. Novel drug targets, or drug combinations that induce a synergistic response, would be of great benefit to patients. The identification of genes that are essential for cell survival can be undertaken using functional genomics screens. Furthermore, performing such screens in the presence of a targeted agent would allow the identification of combinations that result in a synthetic lethal interaction...
October 3, 2017: Scientific Data
https://www.readbyqxmd.com/read/28968982/methylation-of-bnip3-in-pancreatic-cancer-inhibits-the-induction-of-mitochondrial-mediated-tumor-cell-apoptosis
#13
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...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28966949/protocol-for-establishing-a-multiplex-image-based-autophagy-rnai-screen-in-cell-cultures
#14
Jennifer Jung, Christian Behrends
Autophagy is a recycling pathway, in which intracellular cargoes including protein aggregates and bacteria are engulfed by autophagosomes and subsequently degraded after fusion with lysosomes. Dysregulation of this process is involved in several human diseases such as cancer or neurodegeneration. Hence, advancing our understanding of how autophagy is regulated provides an opportunity to explore druggable targets and subsequently develop treatment strategies for these diseases. To identify novel autophagy regulators, we developed an image-based phenotypic RNAi screening approach using autophagic marker proteins at endogenous levels (Jung et al...
September 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28963376/poly-r-c-binding-protein-pcbp-1-expression-is-regulated-by-the-e3-ligase-ube4a-in-thyroid-carcinoma
#15
Ming-Peng Zhang, Wei-San Zhang, Jin Tan, Ming-Hui Zhao, Lin-Juan Lian, Jie Cai
Thyroid cancer patients with high miR-490-3p inhibits translation of PCBP1 mRNA, whereas in patients with low miR-490-3p PCBP1 mRNA expression is high; however, the resultant   protein is targeted for degradation through the proteasome. The objective of the current study was to evaluate the molecular mechanism that regulates post-translation degradation of PCBP1 expression in thyroid cancer cells. Mass spectrometric analysis of PCBP1 immunoprecipitates from MG-132 treated TPC1 cells revealed a list of ubiquitin ligases associated with PCBP1...
September 28, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28960165/recent-advances-in-exosome-based-nanovehicles-as-rna-interference-therapeutic-carriers
#16
Rahul Maheshwari, Muktika Tekade, Piyush Gondaliya, Kiran Kalia, Antony D'Emanuele, Rakesh Kumar Tekade
RNA interference (RNAi) therapeutics (siRNA, miRNA, etc.) represent an emerging medicinal remedy for a variety of ailments. However, their low serum stability and low cellular uptake significantly restrict their clinical applications. Exosomes are biologically derived nanodimensional vesicle ranging from a few nanometers to a hundred. In the last few years, several reports have been published demonstrating the emerging applications of these exogenous membrane vesicles, particularly in carrying different RNAi therapeutics to adjacent or distant targeted cells...
September 29, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28959421/regulation-and-imaging-of-gene-expression-via-an-rna-interference-antagonistic-biomimetic-probe
#17
Kai Zhang, Xue-Jiao Yang, Wei Zhao, Ming-Chen Xu, Jing-Juan Xu, Hong-Yuan Chen
Regulation of gene expression is highly important in the area of cell biology. In this work a novel convenient and versatile strategy is reported which permits both gene regulation and imaging in living cells. An oligonucleotide-based biomimetic probe was designed to target an RNA-induced silencing complex (RISC) and served as an agent for the modulation of c-Myc protein expression in living cells through regulating the RNA interference (RNAi) pathway. In this probe, a DNA strand (Strand1) serving as the frame was immobilized on a AuNP with a thiol group at the 5' end...
July 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28955982/therapeutic-potential-of-gw501516-and-the-role-of-peroxisome-proliferator-activated-receptor-%C3%AE-%C3%AE-and-b-cell-lymphoma-6-in-inflammatory-signaling-in-human-pancreatic-cancer-cells
#18
Russell W Smith, Jeffrey D Coleman, Jerry T Thompson, John P Vanden Heuvel
Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a member of the nuclear receptor superfamily and a ligand-activated transcription factor that is involved in the regulation of the inflammatory response via activation of anti-inflammatory target genes and ligand-induced disassociation with the transcriptional repressor B-cell lymphoma 6 (BCL6). Chronic pancreatitis is considered to be a significant etiological factor for pancreatic cancer development, and a better understanding of the underlying mechanisms of the transition between inflammation and carcinogenesis would help further elucidate chemopreventative options...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28947735/a-role-for-tau-protein-in-maintaining-ribosomal-dna-stability-and-cytidine-deaminase-deficient-cell-survival
#19
Elias Bou Samra, Géraldine Buhagiar-Labarchède, Christelle Machon, Jérôme Guitton, Rosine Onclercq-Delic, Michael R Green, Olivier Alibert, Claude Gazin, Xavier Veaute, Mounira Amor-Guéret
Cells from Bloom's syndrome patients display genome instability due to a defective BLM and the downregulation of cytidine deaminase. Here, we use a genome-wide RNAi-synthetic lethal screen and transcriptomic profiling to identify genes enabling BLM-deficient and/or cytidine deaminase-deficient cells to tolerate constitutive DNA damage and replication stress. We found a synthetic lethal interaction between cytidine deaminase and microtubule-associated protein Tau deficiencies. Tau is overexpressed in cytidine deaminase-deficient cells, and its depletion worsens genome instability, compromising cell survival...
September 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28947497/gain-of-function-mutant-p53-activates-small-gtpase-rac1-through-sumoylation-to-promote-tumor-progression
#20
Xuetian Yue, Cen Zhang, Yuhan Zhao, Juan Liu, Alan W Lin, Victor M Tan, Justin M Drake, Lianxin Liu, Michael N Boateng, Jun Li, Zhaohui Feng, Wenwei Hu
Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1...
August 15, 2017: Genes & Development
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