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https://www.readbyqxmd.com/read/29792692/small-molecule-targeted-recruitment-of-a-nuclease-to-rna
#1
Matthew G Costales, Yasumasa Matsumoto, Sai Pradeep Velagapudi, Matthew D Disney
The choreography between RNA synthesis and degradation is a key determinant in biology. Engineered systems such as CRISPR have been developed to rid a cell of RNAs. Here, we show that a small molecule can recruit a nuclease to a specific transcript, triggering its destruction. A small molecule that selectively binds the oncogenic microRNA(miR)-96 hairpin precursor was appended with a short 2'-5' poly(A) oligonucleotide. The conjugate locally activated endogenous, latent ribonuclease (RNase L), which selectively cleaved the miR-96 precursor in cancer cells in a catalytic and sub-stoichiometric fashion...
May 24, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29792386/disparate-effects-of-shb-gene-deficiency-on-disease-characteristics-in-murine-models-of-myeloid-b-cell-and-t-cell-leukemia
#2
Maria Jamalpour, Xiujuan Li, Karin Gustafsson, Jeffrey W Tyner, Michael Welsh
The Src homology-2 domain protein B is an adaptor protein operating downstream of tyrosine kinases. The Shb gene knockout has been found to accelerate p210 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced leukemia. In human myeloid leukemia were tumors with high Src homology-2 domain protein B mRNA content, tumors were, however, associated with decreased latency and myeloid leukemia exhibiting immune cell characteristics. Thus, the aim of this study was to investigate the effects of Shb knockout on the development of leukemia in three additional models, that is, colony stimulating factor 3 receptor-T618I-induced neutrophilic leukemia, p190 Breakpoint cluster region-cAbl oncogene 1 tyrosine kinase-induced B-cell leukemia, and G12D-Kras-induced T-cell leukemia/thymic lymphoma...
April 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29791870/myc-induced-metabolic-stress-and-tumorigenesis
#3
REVIEW
Adam J Wolpaw, Chi V Dang
The MYC oncogene is commonly altered across human cancers. Distinct from the normal MYC proto-oncogene, which is under tight transcriptional, translational, and post-translational control, deregulated oncogenic MYC drives imbalanced, non-linear amplification of transcription that results in oncogenic 'stress.' The term 'stress' had been a euphemism for our lack of mechanistic understanding, but synthesis of many studies over the past decade provides a more coherent picture of oncogenic MYC driving metastable cellular states, particularly altered metabolism, that activate and depend on cellular stress response pathways to allow for continued growth and survival...
May 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29791786/matrine-suppresses-kras-driven-pancreatic-cancer-growth-by-inhibiting-autophagy-mediated-energy-metabolism
#4
Young-Ra Cho, Ji Hyeon Lee, Ji Hye Kim, So-Yeon Lee, Suna Yoo, Min-Kyo Jung, Su Jung Kim, Hyun Ju Yoo, Chang-Gi Pack, Jin Kyung Rho, Jaekyoung Son
Matrine is a natural compound extracted from the herb Sophora flavescens Ait which is widely used in traditional Chinese medicine for treating various diseases. Recently, matrine was reported to have antitumor effects against a variety of cancers without any obvious side effects; however, the molecular mechanisms of its antiproliferative effects on cancer are unclear. Here, we report that matrine inhibits autophagy-mediated energy metabolism, which is necessary for pancreatic cancer growth. We found that matrine significantly reduces pancreatic cancer growth in vitro and in vivo by insufficiently maintaining mitochondrial metabolic function and energy level...
May 23, 2018: Molecular Oncology
https://www.readbyqxmd.com/read/29791781/a-dual-role-of-mir-22-in-rhabdomyolysis-induced-acute-kidney-injury-aki
#5
Susanne Mathia, Lucas J Rudigier, Mumtaz Kasim, Karin M Kirschner, Pontus B Persson, Kai-Uwe Eckardt, Christian Rosenberger, Michael Fähling
AIM: In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we studied miR-22, a potential HIF repressor, in normal kidneys, as well as in rhabdomyolysis-induced AKI, a condition where miR-22 is up-regulated. METHODS: AKI in mice was provoked by IM injection of glycerol. Tissue homogenates were processed to determine the levels of candidate RNAs and proteins, as well as global gene expression profiles...
May 23, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29791595/microrna-3129-promotes-cell-proliferation-in-gastric-cancer-cell-line-sgc7901-via-positive-regulation-of-prb
#6
Shaofeng Yang, Nan Sheng, Lili Pan, Jing Cao, Jiao Liu, Ran Ma
Several microRNAs (miRNAs) have been reported as oncogenes or tumor suppressors in many cancers, including gastric cancer (GC). However, the role and molecular mechanism of miR-3129 in GC is largely unknown. We aimed to explore the function and the underlying molecular mechanism of miR-3129 in GC. Cancer tissues and corresponding adjacent tissues were collected from 50 patients with GC, and the expression of miR-3129 was detected by RT-qPCR. The expression of miR-3129 and pRb in human GC cell line SCG7091 was altered by transient transfection...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29790789/assessment-of-the-association-between-the-frequency-of-micronucleus-and-p-16ink4a-ki-67-co-expression-in-patients-with-cervical-intraepithelial-lesions
#7
G Gashi, V Mahovlić, E Bahtiri, F Kurshumliu, A Podrimaj-Bytyqi, I R Elezaj
Human papilloma virus (HPV) infection is the main etiological factor for cervical intraepithelial lesions (CIN). An important characteristic of this process is the loss of genome stability. Therefore, it is imperative to use biomarkers of DNA damage caused by genomic instability to identify high risk individuals. We investigated the frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) of 20 patients, diagnosed as histologically CIN 1 and 10 healthy controls. We also examined the frequency of other nuclear anomalies including nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in PBL of patients with CIN 1 and healthy controls, and evaluated the benefits of p16INK4a and Ki-67 (p16INK4a /Ki-67) immunohistochemical double staining for identifying cervical squamous cells that express HPV E6/E7 oncogenes...
May 23, 2018: Biotechnic & Histochemistry: Official Publication of the Biological Stain Commission
https://www.readbyqxmd.com/read/29790665/long-noncoding-rna-ufc1-is-activated-by-e2f1-and-exerts-oncogenic-properties-by-functioning-as-a-cerna-of-foxp3
#8
Jie Xi, Jing Feng, Saitian Zeng, Ping Huang
Cervical cancer is one of the most common gynecologic cancers around the world. Long noncoding RNAs (lncRNAs) are considered to be important regulators of some biological processes. Recently, it has been reported that linc-UFC1 is a putative oncogene in some cancers. However, the functional roles of linc-UFC1 have not been investigated in cervical cancer. Here, it was demonstrated that linc-UFC1 expression was significantly increased in cervical cancer tissues, and its overexpression was associated with the poor survival of patients with cervical cancer...
May 23, 2018: Cancer Medicine
https://www.readbyqxmd.com/read/29790306/the-role-of-novel-prognostic-markers-prox1-and-foxc2-in-carcinogenesis-of-oral-squamous-cell-carcinoma
#9
Neha S Agnihotri, Madhusudan Astekar
Oral squamous cell carcinoma is the most common malignant tumor of the head and neck regions and accounts for more than 90% of cancers in the oral cavity. The angiogenesis, lymphangiogenesis and epithelial mesenchymal transition are known to be pivotal for tumor progression and metastasis. In the last decade, much data has been generated concerning the molecular mechanisms of angiogenesis, lymphangiogenesis and its significance in pathological conditions. The main angiogenic and lymphangiogenic factors have been identified as vascular endothelial growth factor A (VEGF-A), vascular endothelial growth factor receptor 2 (VEGFR-2), forkhead box (FOX) C2 while vascular endothelial growth factor C/D (VEGF-C/D), vascular endothelial growth factor receptor 3 (VEGFR-3), Prospero homeobox 1 (PROX1), LYVE-1, podoplanin, Tie/Angioprotein (Ang) 2 and EphrinB2 respectively...
May 2018: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/29790086/testosterone-mediated-activation-of-androgenic-signalling-sustains-in-vitro-the-transformed-and-radioresistant-phenotype-of-rhabdomyosarcoma-cell-lines
#10
S Giannattasio, F Megiorni, V Di Nisio, A Del Fattore, R Fontanella, S Camero, C Antinozzi, C Festuccia, G L Gravina, S Cecconi, C Dominici, L Di Luigi, C Ciccarelli, P De Cesaris, A Riccioli, B M Zani, A Lenzi, R G Pestell, A Filippini, C Crescioli, V Tombolini, F Marampon
PURPOSE: Rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in childhood, rarely affects adults, preferring male. RMS expresses the receptor for androgen (AR) and responds to androgen; however, the molecular action of androgens on RMS is unknown. METHODS: Herein, testosterone (T) effects were tested in embryonal (ERMS) and alveolar (ARMS) RMS cell lines, by performing luciferase reporter assay, RT-PCR, and western blotting experiments. RNA interference experiments or bicalutamide treatment was performed to assess the specific role of AR...
May 22, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29789998/the-expression-and-role-of-lncrna-ax800134-in-hepatitis-b-virus-related-hepatocellular-carcinoma
#11
Kai Zuo, Li Kong, Dong Xue, Yanyan Yang, Linlin Xie
Chronic infection with hepatitis B virus (HBV) is one of most important risk factors for the development of hepatocellular carcinoma (HCC). Several long non-coding RNAs (lncRNAs) have been shown to be involved in the etiology of HBV-related HCC. AX800134 is one recently identified lncRNA associated with HCC. In this study, we validated the upregulated expression of AX800134 in HBV-positive HCC compared with HBV-negative HCC. Furthermore, we found that HBV X protein (HBx) directly triggered AX800134 expression in human hepatoma HepG2 cells...
May 22, 2018: Virus Genes
https://www.readbyqxmd.com/read/29789714/estrogen-receptor-%C3%AE-promotes-renal-cell-carcinoma-progression-via-regulating-lncrna-hotair-mir-138-200c-204-217-associated-cerna-network
#12
Jie Ding, Chiuan-Ren Yeh, Yin Sun, Changyi Lin, Joshua Chou, Zhenyu Ou, Chawnshang Chang, Jun Qi, Shuyuan Yeh
Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression...
May 23, 2018: Oncogene
https://www.readbyqxmd.com/read/29789623/mir-29c-reduces-the-cisplatin-resistance-of-non-small-cell-lung-cancer-cells-by-negatively-regulating-the-pi3k-akt-pathway
#13
Dian-Min Sun, Bu-Fu Tang, Zhen-Xiang Li, Hong-Bo Guo, Jin-Ling Cheng, Ping-Ping Song, Xin Zhao
In previous studies, miR-29s showed tumor suppressor properties against lung cancer, which improved the survival of patients upon the administration of chemotherapy via an unknown mechanism. Here, we investigated the regulatory effects of miR-29s on the cisplatin resistance of NSCLC cells. The expression of miR-29s was assessed in 130 clinical patients and in cisplatin-treated NSCLS cell lines. MiR-29c expression was decreased in 77% of NSCLC patients. Cisplatin treatment increased the expression of miR-29c and decreased the expression of its oncogenic target AKT2 in NSCLC cell lines...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789104/functionalized-caprolactone-polyethylene-glycol-based-thermo-responsive-hydrogels-of-silibinin-for-the-treatment-of-malignant-melanoma
#14
Behzad Sharif Makhmalzadeh, Ommoleila Molavi, Mohammad Reza Vakili, Hai-Feng Zhang, Amir Solimani, Hoda Soleymani Abyaneh, Raimar Loebenberg, Raymond Lai, Afsaneh Lavasanifar
PURPOSE: Silibinin, is a natural compound, which has shown anticancer activity in various malignancies. In this study, we evaluated the anticancer effects of silibinin in B16-F10 melanoma cells and developed a novel thermoresponsive hydrogel for local delivery of this compound. METHOD: A thermoresponsive hydrogel loaded with silibinin was prepared using triblock copolymers of poly[(α-benzyl carboxylate-e-caprolactone)-co-(α-carboxyl-e-caprolactone)]ran-b-PEG-b-[(α-benzyl carboxylate-e-caprolactone) -co-(α-carboxyl-e-caprolactone)]ran (PCBCL-b-PEG-b-PCBCL), namely PolyGelTM, and compared with a Pluronic F-127 formulation of silibinin...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29788890/inhibition-of-pyruvate-dehydrogenase-kinase-as-a-therapeutic-strategy-against-cancer
#15
Swatishree Sradhanjali, Mamatha M Reddy
Cancer cells alter their metabolism to support the uninterrupted supply of biosynthetic molecules required for continuous proliferation. Glucose metabolism is frequently reprogrammed in several tumors in addition to fatty acid, amino acid and glutamine metabolism. Pyruvate dehydrogenase kinase (PDK) is a gatekeeper enzyme involved in altered glucose metabolism in tumors. There are four isoforms of PDK (1 to 4) in humans. PDK phosphorylates E1α subunit of pyruvate dehydrogenase complex (PDC) and inactivates it...
May 22, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29788731/claudin-7-cldn7-is-overexpressed-in-gastric-cancer-and-promotes-gastric-cancer-cell-proliferation-invasion-and-maintains-mesenchymal-state
#16
Z Wu, J Shi, Y Song, J Zhao, J Sun, X Chen, P Gao, Z Wang
Gastric cancer (GC) ranks as the fourth most common cancer worldwide and is among the most aggressive types of cancer. Claudin-7 (CLDN7) has been found to be aberrantly expressed in some types of cancers. However, the expression and role of CLDN7 on gastric cancer (GC) remain largely unknown. In this study, we have performed the largest expression analysis study to date of CLDN7 in 113 pairs of human GC tissues and non-tumorous adjacent tissues. We found CLDN7 expression is significantly elevated in GC tissues, and the overexpression of CLDN7 is closely related to lymph node metastasis...
March 14, 2018: Neoplasma
https://www.readbyqxmd.com/read/29788550/usp22-acts-as-an-oncoprotein-to-maintain-glioma-malignancy-through-deubiquitinating-bmi1-for-stabilization
#17
Guan-Zhong Qiu, Xiao-Yuan Mao, Yue Ma, Xing-Chun Gao, Zhen Wang, Ming-Zhu Jin, Wei Sun, Yong-Xiang Zou, Jing Lin, Hua-Lin Fu, Wei-Lin Jin
USP22 is a member of "death-from-cancer" signature, which plays a key role in cancer progression. Although previous evidence has shown that USP22 is overexpressed and correlated with poor prognosis in glioma. The effect and mechanism of USP22 in glioma malignancy especially cancer stemness remain elusive. Here, we find USP22 is more enriched in stem-like tumorspheres than differentiated glioma cells. USP22 knockdown inhibits cancer stemness in glioma cell lines. With a cell-penetrating TAT-tag protein, BMI1, a robust glioma stem-cell marker, is found to mediate the effect of USP22 on glioma stemness...
May 22, 2018: Cancer Science
https://www.readbyqxmd.com/read/29787863/validity-of-targeted-next-generation-sequencing-in-routine-care-for-identifying-clinically-relevant-molecular-profiles-in-non-small-cell-lung-cancer-results-of-a-2-year-experience-on-1-343-samples
#18
Antoine Legras, Marc Barritault, Anne Tallet, Elizabeth Fabre, Alice Guyard, Bastien Rance, William Digan, Nicolas Pecuchet, Etienne Giroux-Leprieur, Catherine Julie, Stéphane Jouveshomme, Véronique Duchatelle, Véronique Giraudet, Laure Gibault, Alain Cazier, Jean Pastre, Françoise LE Pimpec-Barthes, Pierre Laurent-Puig, Hélène Blons
Theranostic assays are based on single gene testing but the ability of next-generation sequencing (NGS) to interrogate numerous genetic alterations will progressively replace single gene assays. Although NGS was evaluated to screen for theranostic mutations, its usefulness in clinical practice on large series of samples remains to be demonstrated. NGS performance was assessed following guidelines. TaqMan probes and NGS were compared for their ability to detect EGFR and KRAS mutations and NGS mutation profiles were analyzed on a large series of NSCLC (n=1,343)...
May 19, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29787820/clinicopathological-characteristics-of-thyroid-transcription-factor-1-negative-small-cell-lung-cancers
#19
Yuko Iida, Shinobu Masuda, Yoko Nakanishi, Tetsuo Shimizu, Haruna Nishimaki, Mai Takahashi, Mari Hikichi, Shuichiro Maruoka, Yasuhiro Gon, Noriaki Takahashi, Shu Hashimoto
Limitations in obtaining surgically resected or biopsy samples of small cell lung cancer (SCLC) tumors make comprehensive biological analyses difficult. The loss of thyroid transcription factor 1 (TTF-1) has been associated with the aggressive behavior of non-small cell lung cancer (NSCLC); however, clinicopathological features of TTF-1-negative SCLC remain unclear. This study aimed to elucidate the characteristics of TTF-1-negative SCLC. We studied the associations between the expression of TTF-1 and the clinicopathological factors associated with SCLC, including survival and expression of neuroendocrine markers (synaptophysin, chromogranin A, and CD56), neuroendocrine cell-specific transcription factors (achaete-scute homolog like 1 (ASCL1), BRN2), a proliferation marker (Ki-67 labeling index), and an oncogene (Nuclear Factor 1B (NF1B))...
May 19, 2018: Human Pathology
https://www.readbyqxmd.com/read/29786791/protocols-for-studies-on-tmprss2-erg-in-prostate-cancer
#20
Hubert Pakula, Douglas E Linn, Daniel R Schmidt, Marit Van Gorsel, Matthew G Vander Heiden, Zhe Li
TMPRSS2/ERG is the most common type of gene fusions found in human prostate cancer. There are two important features of TMPRSS2/ERG fusions. One is that these gene fusions lead to ectopic expression of ERG, an ETS family transcription factor, in prostate epithelial cells from the 5' control region of an androgen/estrogen dual-responsive gene, TMPRSS2; the other is that ~60% of these fusions are generated via intrachromosomal deletion of the interstitial region between TMPRSS2 and ERG. To recapitulate these important aspects of TMPRSS2/ERG fusions, we generated several TMPRSS2/ERG knockin mouse models based on the endogenous Tmprss2 locus...
2018: Methods in Molecular Biology
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