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https://www.readbyqxmd.com/read/29452948/photo-tearable-tape-close-wrapped-upconversion-nanocapsules-for-near-infrared-modulated-efficient-sirna-delivery-and-therapy
#1
Yue Zhang, Kewei Ren, Xiaobo Zhang, Zhicong Chao, Yuqin Yang, Deju Ye, Zhihui Dai, Ying Liu, Huangxian Ju
RNA interference (RNAi) has become an appealing therapeutic approach for cancer and other diseases. One key challenge is the effective protection of these small fragile biomolecules against complicated physiological environments as well as efficient on-demand release. Here we design a photo-tearable polymer tape close-wrapped nanocapsule for efficient NIR modulated siRNA delivery. The photo-tearable nanocapsules comprise core-shell upconversion nanoparticles (UCNPs) coated with mesoporous silica layer for loading of photosensitizer hypocrellin A (HA) and small interfering RNA (siRNA) against polo-like kinase 1 (PLK1), and covalently bound thin membranes of polyethylene glycol (PEG) via a synthesized photocleavable linker (PhL)...
February 9, 2018: Biomaterials
https://www.readbyqxmd.com/read/29452216/upregulation-of-tiam1-contributes-to-cervical-cancer-disease-progression-and-indicates-poor-survival-outcome
#2
Yang Yang, Qunying Wu, Nan Li, Shuanlong Che, Tiefeng Jin, Yunze Nan, Zhenhua Lin, Liyan Chen
T lymphoma invasion and metastasis 1 (Tiam1), a guanine nucleotide exchange factor, is involved in the tumorigenesis of a number of malignancies. This study was aimed to explore the role of Tiam1 in cervical cancer progression, and evaluate the prognostic values. Tiam1 protein expression levels were detected by immunohistochemical (IHC) staining in 174 cervical cancer tissues, 92 of CINs (Cervical intraepithelial neoplasia) and 32 of normal cervical epithelia tissues. Clinicopathological parameters and overall survival data were collected and compared between different Tiam1 statuses...
February 13, 2018: Human Pathology
https://www.readbyqxmd.com/read/29449693/tumor-cell-intrinsic-tim-3-promotes-liver-cancer-via-nf-%C3%AE%C2%BAb-il-6-stat3-axis
#3
Hualin Zhang, Yang Song, Huimin Yang, Zhiyan Liu, Lifen Gao, Xiaohong Liang, Chunhong Ma
T-cell immunoglobulin and mucin-domain containing-3 (Tim-3), mediating immune exhaustion in tumor microenvironment, has become a promising target for tumor therapy. However, the exact mechanisms for tumor cell-intrinsic Tim-3 in tumor development and its potential contribution in Tim-3-targeted therapy strategy have not been elucidated yet. In this study, we showed that human liver cancer tissues contained high ratio of Tim-3-expressing hepatocytes, and cytokines rich in tumor microenvironment and HBV involved in Tim-3 upregulation in malignant hepatocytes...
February 16, 2018: Oncogene
https://www.readbyqxmd.com/read/29440447/a-human-genome-wide-rnai-screen-reveals-diverse-modulators-that-mediate-ire1%C3%AE-xbp1-activation
#4
Zhifen Yang, Jing Zhang, Dadi Jiang, Purvesh Khatri, David E Solow-Cordero, Diego A S Toesca, Constantinos Koumenis, Nicholas C Denko, Amato J Giaccia, Quynh-Thu Le, Albert C Koong
Activation of the unfolded protein response (UPR) signaling pathways is linked to multiple human diseases including cancer. The inositol-requiring kinase 1 (IRE1)-X-box binding protein 1 (XBP1) pathway is the most evolutionarily conserved of the three major signaling branches of the UPR. Here, we performed a genome-wide siRNA screen to obtain a systematic assessment of genes integrated in the IRE1-XBP1 axis. We monitored the expression of an XBP1-luciferase chimeric protein in which luciferase was fused in-frame with the spliced (active) form of XBP1...
February 9, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29435942/identification-and-isolation-of-novel-sugar-like-rna-protecting-materials-glycylglycerins-from-pluripotent-stem-cells
#5
Shi-Lung Lin
Pluripotent stem cells are a resourceful treasure box for regenerative medicine. They contain a large variety of novel materials useful for designing and developing new medicines and therapies directed against many aging-associated degenerative disorders, including Alzheimer's disease, Parkinson's disease, stroke, diabetes, osteoporosis, and cancers. Currently, identification of these novel stem cell-specific materials is one of major breakthroughs in the field of stem cell research. Particularly, since the discovery of induced pluripotent stem cells (iPSC) in year 2006, the methods of iPSC derivation further provide an unlimited resource for screening, isolating, and even producing theses novel stem cell-specific materials in vitro...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435927/gene-silencing-in-vitro-and-in-vivo-using-intronic-micrornas
#6
Shi-Lung Lin, Shao-Yao Ying
MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular messenger RNAs (mRNAs) that contain either complete or partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. Numerous miRNAs have been reported to induce RNA interference (RNAi), a post-transcriptional gene-silencing mechanism. Recent evidence also indicates that they are involved in the transcriptional regulation of genome activities. They were first discovered in Caenorhabditis elegans as native RNA fragments that modulate a wide range of genetic regulatory pathways during embryonic development, and are now recognized as small gene silencers transcribed from the noncoding regions of a genome...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29435157/the-microtubule-associated-protein-prc1-is-a-potential-therapeutic-target-for-lung-cancer
#7
Steffen Hanselmann, Patrick Wolter, Jonas Malkmus, Stefan Gaubatz
In this study, we investigated whether proteins that are involved in cytokinesis are potential targets for therapy of lung cancer. We find that the microtubule-associated protein PRC1 (protein required for cytokinesis 1), which plays a key role in organizing anti-parallel microtubule in the central spindle in cytokinesis, is overexpressed in lung cancer cell lines compared to normal cells. Increased expression of PRC1 is correlated with a poor prognosis of human lung adenocarcinoma patients. Lentiviral delivered, inducible RNAi of PRC1 demonstrated that proliferation of lung cancer cell lines strongly depends on PRC1...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29423094/differential-regulation-of-the-androgen-receptor-by-protein-phosphatase-regulatory-subunits
#8
James Grey, Dominic Jones, Laura Wilson, Sirintra Nakjang, Jake Clayton, Richard Temperley, Emma Clark, Luke Gaughan, Craig Robson
The Androgen Receptor (AR) is a key molecule in the development, maintenance and progression of prostate cancer (PC). However, the relationship between the AR and co-regulatory proteins that facilitate AR activity in castrate resistant settings remain understudied. Here we show that protein phosphatase 1 regulatory subunits, identified from a phosphatase RNAi screen, direct PP1 catalytic subunits to a varied yet significant response in AR function. As such, we have characterised the PP1β holoenzyme, myosin phosphatase (MLCP), as a novel ligand independent regulator of the AR...
January 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29422775/down-regulation-of-g-protein-coupled-receptor-137-expression-inhibits-proliferation-and-promotes-apoptosis-in-leukemia-cells
#9
Li-Jie Men, Ji-Zhu Liu, Hai-Ying Chen, Li Zhang, Shuang-Feng Chen, Tai-Wu Xiao, Jing-Xia Wang, Guang-Yao Li, Ya-Ping Wu
Background: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29420561/implication-of-krt16-fam129a-and-hkdc1-genes-as-atf4-regulated-components-of-the-integrated-stress-response
#10
Alexandra G Evstafieva, Irina E Kovaleva, Maria S Shoshinova, Andrei V Budanov, Peter M Chumakov
The ATF4 transcription factor is a key regulator of the adaptive integrated stress response (ISR) induced by various stresses and pathologies. Identification of novel transcription targets of ATF4 during ISR would contribute to the understanding of adaptive networks and help to identify novel therapeutic targets. We were previously searching for genes that display an inverse regulation mode by the transcription factors ATF4 and p53 in response to mitochondrial respiration chain complex III inhibition. Among the selected candidates the human genes for cytokeratine 16 (KRT16), anti-apoptotic protein Niban (FAM129A) and hexokinase HKDC1 have been found highly responsive to ATF4 overexpression...
2018: PloS One
https://www.readbyqxmd.com/read/29417968/engineering-functional-inorganic-organic-hybrid-systems-advances-in-sirna-therapeutics
#11
REVIEW
Jianliang Shen, Wei Zhang, Ruogu Qi, Zong-Wan Mao, Haifa Shen
Cancer treatment still faces a lot of obstacles such as tumor heterogeneity, drug resistance and systemic toxicities. Beyond the traditional treatment modalities, exploitation of RNA interference (RNAi) as an emerging approach has immense potential for the treatment of various gene-caused diseases including cancer. The last decade has witnessed enormous research and achievements focused on RNAi biotechnology. However, delivery of small interference RNA (siRNA) remains a key challenge in the development of clinical RNAi therapeutics...
February 8, 2018: Chemical Society Reviews
https://www.readbyqxmd.com/read/29413418/dise-a-seed-dependent-rnai-off-target-effect-that-kills-cancer-cells
#12
REVIEW
William Putzbach, Quan Q Gao, Monal Patel, Ashley Haluck-Kangas, Andrea E Murmann, Marcus E Peter
Off-target effects (OTEs) represent a significant caveat for RNAi caused by substantial complementarity between siRNAs and unintended mRNAs. We now discuss the existence of three types of seed-dependent OTEs (sOTEs). Type I involves unintended targeting through the guide strand seed of an siRNA. Type II is caused by the activity of the seed on the designated siRNA passenger strand when loaded into the RNA-induced silencing complex (RISC). Both type I and II sOTEs will elicit unpredictable cellular responses...
January 2018: Trends in Cancer
https://www.readbyqxmd.com/read/29402961/itgb1-dependent-upregulation-of-caveolin-1-switches-tgf%C3%AE-signalling-from-tumour-suppressive-to-oncogenic-in-prostate-cancer
#13
Teijo Pellinen, Sami Blom, Sara Sánchez, Katja Välimäki, John-Patrick Mpindi, Hind Azegrouz, Raffaele Strippoli, Raquel Nieto, Mariano Vitón, Irene Palacios, Riku Turkki, Yinhai Wang, Miguel Sánchez-Alvarez, Stig Nordling, Anna Bützow, Tuomas Mirtti, Antti Rannikko, María C Montoya, Olli Kallioniemi, Miguel A Del Pozo
Caveolin-1 (CAV1) is over-expressed in prostate cancer (PCa) and is associated with adverse prognosis, but the molecular mechanisms linking CAV1 expression to disease progression are poorly understood. Extensive gene expression correlation analysis, quantitative multiplex imaging of clinical samples, and analysis of the CAV1-dependent transcriptome, supported that CAV1 re-programmes TGFβ signalling from tumour suppressive to oncogenic (i.e. induction of SLUG, PAI-1 and suppression of CDH1, DSP, CDKN1A). Supporting such a role, CAV1 knockdown led to growth arrest and inhibition of cell invasion in prostate cancer cell lines...
February 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29399086/copb2-suppresses-cell-proliferation-and-induces-cell-cycle-arrest-in-human-colon-cancer-by-regulating-cell-cycle-related-proteins
#14
Yan Wang, Zhi Chai, Min Wang, Yanling Jin, Aijun Yang, Min Li
Coat proteins (COPs), including the major types clathrin, COPI and COPII, play a considerable role in intracellular transport by initiating the formation of transport vesicles. Coatomer protein complex subunit β2 (COPB2) is one of the seven subunits that make up a COPI complex. In the present study, we found that COPB2 was highly expressed in human colon cancer specimens. However, to date, there have been no reports describing the functions of COPB2 in human colon cancer cells. In this study, we analyzed the functions of COPB2 in the proliferation and cell cycle arrest of human RKO and HCT116 colon cancer cells by using lentivirus-mediated RNAi infection...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29393493/inhibition-of-mus81-improves-the-chemical-sensitivity-of-olaparib-by-regulating-mcm2-in-epithelial-ovarian-cancer
#15
Ailing Zhong, Hongqin Zhang, Suhong Xie, Minjie Deng, Hui Zheng, Yanchun Wang, Miaomiao Chen, Renquan Lu, Lin Guo
Dysfunction of the DNA repair pathway contributes to tumorigenesis and drug resistance. Methyl methanesulfonate and ultraviolet sensitive gene clone 81 (MUS81), a key endonuclease in DNA repair, is generally considered a tumor suppressor; however, recent studies have revealed its tumor-promoting effect in epithelial ovarian cancer (EOC) and have shown that its overexpression is associated with cisplatin sensitization. However, the exact functional role of MUS81 and its regulation in relation to chemotherapy sensitivity remains unknown...
January 22, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29393421/effects-of-nuclear-factor%C3%A2-%C3%AE%C2%BAb-on-the-uptake-of-131iodine-and-apoptosis-of-thyroid-carcinoma-cells
#16
Fukun Chen, Shuting Yin, Jialun Zhu, Li Jia, Huaping Zhang, Chuanzhou Yang, Chao Liu, Zhiyong Deng
Thyroid carcinoma is primarily treated by surgery combined with radioactive 131iodine (131I) treatment; however, certain patients exhibit resistance to 131I treatment. Previous research indicated that nuclear factor‑κB (NF‑κB) was associated with resistance to 131I in cancer cells. The present study aimed to investigate the effects of NF‑κB on 131I uptake and apoptosis in thyroid carcinoma cells. TPC‑1 and BCPAP cell lines were employed as research models in the present study, and the expression of NF‑κB was inhibited by RNA interference (RNAi)...
January 25, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29393401/pyruvate-kinase-type-m2-contributes-to-the-development-of-pancreatic-ductal-adenocarcinoma-by-regulating-the-production-of-metabolites-and-reactive-oxygen-species
#17
Misa Yokoyama, Nobuhiro Tanuma, Rie Shibuya, Takeharu Shiroki, Makoto Abue, Kuniharu Yamamoto, Koh Miura, Kazunori Yamaguchi, Ikuro Sato, Keiichi Tamai, Kennichi Satoh
The majority of cancer cells maintain a high glycolytic activity and an increased lactate production, even in a well oxygenated environment. This phenomenon is known as the Warburg effect. Previous studies have revealed that various types of cancer selectively express the pyruvate kinase M2 isoform (PKM2), and that PKM2 plays a pivotal role in the Warburg effect. Although elevated PKM2 levels have been observed in pancreatic cancer and other types of cancer, little is known about the biological function of PKM2...
January 30, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29383635/mirnas-regulate-the-hif-switch-during-hypoxia-a-novel-therapeutic-target
#18
REVIEW
Marcin Serocki, Sylwia Bartoszewska, Anna Janaszak-Jasiecka, Renata J Ochocka, James F Collawn, Rafał Bartoszewski
The decline of oxygen tension in the tissues below the physiological demand leads to the hypoxic adaptive response. This physiological consequence enables cells to recover from this cellular insult. Understanding the cellular pathways that mediate recovery from hypoxia is therefore critical for developing novel therapeutic approaches for cardiovascular diseases and cancer. The master regulators of oxygen homeostasis that control angiogenesis during hypoxia are hypoxia-inducible factors (HIFs). HIF-1 and HIF-2 function as transcriptional regulators and have both unique and overlapping target genes, whereas the role of HIF-3 is less clear...
January 27, 2018: Angiogenesis
https://www.readbyqxmd.com/read/29383166/gram-domain-containing-protein-1b-gramd1b-a-novel-component-of-the-jak-stat-signaling-pathway-functions-in-gastric-carcinogenesis
#19
Puja Khanna, Pei Jou Chua, Belinda Shu Ee Wong, Changhong Yin, Aye Aye Thike, Wei Keat Wan, Puay Hoon Tan, Gyeong Hun Baeg
Dysregulated JAK/STAT signaling has been implicated in the molecular pathogenesis of gastric cancer. However, downstream effectors of STAT signaling that facilitate gastric carcinogenesis remain to be explored. We previously identified the Drosophila ortholog of human GRAMD1B in our genome-wide RNAi screen to identify novel components of the JAK/STAT signaling pathway in Drosophila. Here, we examined the involvement of GRAMD1B in JAK/STAT-associated gastric carcinogenesis. We found that GRAMD1B expression is positively regulated by JAK/STAT signaling and GRAMD1B inhibition decreases STAT3 levels, suggesting the existence of a positive feedback loop...
December 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29382922/arhgef39-promotes-tumor-progression-via-activation-of-rac1-p38-mapk-atf2-signaling-and-predicts-poor-prognosis-in-non-small-cell-lung-cancer-patients
#20
Haijing Zhou, Lin Cai, Xiupeng Zhang, Ailin Li, Yuan Miao, Qingchang Li, Xueshan Qiu, Enhua Wang
Rho guanine nucleotide exchange factor 39 (ARHGEF39), also called C9orf100, is a new member of the Dbl-family of guanine nucleotide exchange factors. Although ARHGEF39 has been proven to regulate tumor progression in hepatocellular carcinoma, the downstream signaling pathway of ARHGEF39 and its clinical associations in non-small cell lung cancer (NSCLC) are currently unknown. In the present study, using MTT, colony formation, flow cytometry, mice xenografts, wound healing, and transwell assays, we showed that ARHGEF39 promoted tumor proliferation, migration, and invasion...
January 30, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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