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https://www.readbyqxmd.com/read/28743511/raf-1-ck2-and-rhoa-rock-signaling-promote-tnf-%C3%AE-mediated-endothelial-apoptosis-via-regulating-vimentin-cytoskeleton
#1
Lifeng Yang, Lian Tang, Fan Dai, Guoliang Meng, Runting Yin, Xiaole Xu, Wenjuan Yao
Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α...
July 22, 2017: Toxicology
https://www.readbyqxmd.com/read/28729631/therapeutic-effects-of-long-circulating-mir-135a-containing-cationic-immunoliposomes-against-gallbladder-carcinoma
#2
Guanghua Yang, Baobing Yin
Gallbladder carcinoma (GBC) is the most common malignant tumour in the biliary tract, but effective therapeutics are lacking. Based on our previous studies, miR-135a is a potential tool to inhibit GBC proliferation. In this study, we constructed miR-135a-loaded DSPE-PEG2000 liposomes modified with Anti-EGFR antibodies (Anti-EGFR-CIL-miR-135a). The results of an analysis of their physicochemical properties indicated the particle size of it was 222.0 ± 2.1 nm in diameter with an uptake efficiency of 86...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28709411/rho-kinase-proteins-display-aberrant-upregulation-in-vascular-tumors-and-contribute-to-vascular-tumor-growth
#3
Clarissa N Amaya, Dianne C Mitchell, Brad A Bryan
BACKGROUND: The serine/threonine protein kinases ROCK1 and 2 are key RhoA-mediated regulators of cell shape and cytoskeletal dynamics. These proteins perform multiple functions in vascular endothelial cell physiology and are attractive targets for cancer therapy based on their roles as oncogenes and metastatic promoters. Given their critical functions in both of these processes, we hypothesized that molecular targeting of ROCK proteins would be exceedingly effective against vascular tumors such as hemangiomas and angiosarcomas, which are neoplasms composed of aberrant endothelial cells...
July 14, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28684968/effects-of-total-flavone-from-rhododendron-simsii-planch-flower-on-postischemic-cardiac-dysfunction-and-cardiac-remodeling-in-rats
#4
Xinqi Cheng, Jie Zhang, Zhiwu Chen
This study investigated the effect of total flavone from Rhododendron simsii Planch. flower (TFR) on postischemic cardiac dysfunction and ventricular remodeling and was to test the hypothesis that TFR has an antiventricular remodeling effect through inhibition of urotensin-II receptor- (UTR-) mediated activation of RhoA-ROCK pathways. Twenty-four hours after ligation of the left anterior descending coronary artery, male Sprague-Dawley rats were randomized to receive 4-week treatment with saline (model group) or TFR...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28656312/nogo-receptor-knockdown-and-ciliary-neurotrophic-factor-attenuate-diabetic-retinopathy-in-streptozotocin-induced-diabetic-rats
#5
Xiliang Guo, Xuezheng Liu
Diabetic retinopathy (DR) is a common complication of diabetes mellitus (DM). We investigated whether Nogo receptor (NgR) knockdown and ciliary neurotrophic factor (CNTF) treatment, either alone or in combination, ameliorated diabetic retinopathy (DR) in diabetic rat model. STZ‑induced diabetic rats were administrated for a total of 12 weeks with 3 µM siRNA (5 µl) once every 6 weeks and/or 1 µg CNTF weekly. The retinal tissues were excised. We measured cell number in ganglion cell layer (GCL) using H&E staining and cell apoptosis using TUNEL assay...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28656254/microrna-150-targets-rho-associated-protein-kinase-1-to-inhibit-cell-proliferation-migration-and-invasion-in-papillary-thyroid-carcinoma
#6
Lixia Cheng, Ruixiu Zhou, Min Chen, Linan Feng, Hongyan Li
Thyroid cancer is the most prevalent malignant tumor of the endocrine organs and accounts for one third of all head and neck tumors. Dysregulation of microRNAs is well‑known to contribute to the development of various cancers, including papillary thyroid carcinoma (PTC), which accounts for 80‑90% of all thyroid cancer cases. The present study aimed to investigate the expression, functional roles of microRNA‑150 (miR‑150) and its direct target gene in PTC. miR‑150 expression in PTC tissues and cell lines was analyzed by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR)...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28653610/downregulation-of-microrna-152-and-inhibition-of-cell-proliferation-migration-and-invasion-in-breast-cancer
#7
Adilijiang Maimaitiming, Ailijiang Wusiman, Abulajiang Aimudula, Tuhetiaji Tudahong, Dilimulati Aisimutula
The aim of the present study was to investigate the roles of microRNA-152 (miR-152) in breast cancer initiation and progression. Expression levels of miR-152 were detected in human breast cancer tissues and in a panel of human breast cancer cell lines. In this study, analyzing miR-152 expression by qRT-PCR showed that it was remarkably down-regulated in breast cancer tissues and cell lines. Enforced miR-152 expression suppressed cell proliferation, migration and invasion of breast cancer. Moreover, ROCK1 was identified as a direct and functional target gene of miR-152 in breast cancer using luciferase assay...
June 15, 2017: Oncology Research
https://www.readbyqxmd.com/read/28650862/the-potential-combinational-effect-of-mir-34a-with-celecoxib-in-osteosarcoma
#8
Xia Chen, Dan Peng, Yi Shen, Bo Liu, Hongkang Zhou, Huai Tao, Jufang Huang
Advanced osteosarcoma (OS) is usually treated by preoperative and postoperative chemotherapy, but there are a very limited number of active agents. Celecoxib (Cel) is a COX-2-selective nonsteroidal anti-inflammatory drug and its antitumoral effect has been shown widely in a variety of cancers including OS cells in vitro. However, the potential combinational effect of Cel with other biological therapy has not been reported in OS cells. In this study, the effects of Cel, miR-34a mimics, and their combination on cell proliferation (MTT assay), migration (in-vitro scratch assay), invasion (transwell assay), mRNA (real-time PCR), and protein (Western blot) expression of associated signal transductions were investigated in cultured MG63 cells...
June 23, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28650698/the-rock-isoforms-differentially-regulate-the-morphological-characteristics-of-carcinoma-cells
#9
Rachel J Jerrell, Mitchell J Leih, Aron Parekh
Rho-associated kinase (ROCK) activity drives cell migration via actomyosin contractility. During invasion, individual cancer cells can transition between two modes of migration, mesenchymal and amoeboid. Changes in ROCK activity can cause a switch between these migration phenotypes which are defined by distinct morphologies. However, recent studies have shown that the ROCK isoforms are not functionally redundant as previously thought. Therefore, it is unclear whether the ROCK isoforms play different roles in regulating migration phenotypes...
June 26, 2017: Small GTPases
https://www.readbyqxmd.com/read/28650466/ror2-mediated-alternative-wnt-signaling-regulates-cell-fate-and-adhesion-during-mammary-tumor-progression
#10
K Roarty, A D Pfefferle, C J Creighton, C M Perou, J M Rosen
Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt β-catenin-dependent signaling activity and non-canonical β-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28632992/targeting-the-rhogtpase-rock-pathway-for-the-treatment-of-vhl-hif-pathway-driven-cancers
#11
Jordan M Thompson, Jaime Landman, Olga V Razorenova
The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK 1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. As a function of the later effect, we recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation...
June 20, 2017: Small GTPases
https://www.readbyqxmd.com/read/28609185/discovery-and-preclinical-development-of-netarsudil-a-novel-ocular-hypotensive-agent-for-the-treatment-of-glaucoma
#12
Cheng-Wen Lin, Bryan Sherman, Lori A Moore, Carmen L Laethem, Da-Wen Lu, Padmanabhan P Pattabiraman, Ponugoti Vasantha Rao, Mitchell A deLong, Casey C Kopczynski
PURPOSE: Rho-associated protein kinase (ROCK) inhibitors lower intraocular pressure (IOP) by increasing aqueous outflow through the trabecular meshwork (TM). The preclinical characterization of netarsudil, a new ROCK/norepinephrine transporter (NET) inhibitor currently in clinical development, is presented herein. METHODS: The kinase inhibitory activity of netarsudil was compared to its esterase metabolite, netarsudil-M1, and 3 other ROCK inhibitors using a commercially available kinase assay kit...
June 13, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28608941/tgf-%C3%AE-stimulates-expression-of-chondroitin-polymerizing-factor-in-nucleus-pulposus-cells-through-the-smad3-rhoa-rock1-and-mapk-signaling-pathways
#13
Bo Hu, Chen Xu, Peng Cao, Ye Tian, Ying Zhang, Changgui Shi, Jun Xu, Wen Yuan, Huajiang Chen
The enzyme chondroitin polymerizing factor (ChPF) is primarily involved in extension of the chondroitin sulfate backbone required for the synthesis of sulfated glycosaminoglycan (sGAG). Transforming growth factor beta (TGF-β) upregulates sGAG synthesis in nucleus pulposus cells; however, the mechanisms mediating this induction are incompletely understood. Our study demonstrated that ChPF expression was negatively correlated with the grade of degenerative intervertebral disc disease. Treatment of nucleus pulposus cells with TGF-β induced ChPF expression and enhanced Smad2/3, RhoA/ ROCK activation, and the JNK, p38 and ERK1/2 MAPK signaling pathways...
June 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28598808/mir-199a-b-5p-inhibits-hepatocellular-carcinoma-progression-by-post-transcriptionally-suppressing-rock1
#14
Yangyang Zhan, NanXin Zheng, Fei Teng, Leilei Bao, Fang Liu, Mingjian Zhang, Meng Guo, Wenyuan Guo, Guoshan Ding, Quanxing Wang
In this study, we explored the actions of miR-199a/b-5p during hepatocellular carcinoma (HCC) progression and its potential target genes. Through heatmap miRNA expression analysis of 15 matched HCC tumor and adjacent non-tumor liver tissues from the TCGA database, we detected 19 mRNAs that were upregulated and 13 that were downregulated specifically in HCC. Among these, miR-199 family members were downregulated in HCC tumors and cell lines, as compared to controls. Low miR-199a/b-5p expression was also associated with poor overall survival of HCC patients...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28576719/phenolic-derivatives-from-blaps-japanensis-and-their-biological-evaluation
#15
REVIEW
Tao Zheng, Yong-Ming Yan, Zheng-Chao Tu, Qi Luo, Fu-Rong Xu, Yong-Xian Cheng
This study was designed to characterize compounds from two thousands of insects of Blaps japanensis. With this purpose, pipajiains A-C (1-3), three novel phenolic derivatives, pipajiains D (4) and E (5), two new natural occurring compounds, and four known substances were isolated thereof. Their structures were identified by spectroscopic methods. Biological activities of all these compounds towards EV71, tuberculosis, COX-2, ROCK1/2, and JAK3 kinases were evaluated.
May 30, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28558357/long-non-coding-rna-hoxa11-as-functions-as-a-competing-endogenous-rna-to-regulate-rock1-expression-by-sponging-mir-124-3p-in-osteosarcoma
#16
Mingxing Cui, Jingyu Wang, Qingjiang Li, Junlei Zhang, Jinling Jia, Xinli Zhan
Long non-coding RNAs (lncRNAs) have been strongly associated with various types of cancer. this study was to explore the critical role of lncRNA HOXA11-AS in osteosarcoma (OS) progression. Briefly, we should that the expression of HOXA11-AS was upregulated in OS tissues and cell lines. The high expression of HOXA11-AS was associated with advanced clinical stage, distant metastasis and poor overall survival of OS. In addition, We found that HOXA11-AS silencing suppressed OS cells proliferation, invasion and induced cell arrest in G0/G1 phase...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28533114/2-aminomethylthieno-3-2-d-pyrimidin-4-3h-ones-bearing-3-methylpyrazole-hinge-binding-moiety-highly-potent-selective-and-time-dependent-inhibitors-of-cdc7-kinase
#17
Osamu Kurasawa, Misaki Homma, Yuya Oguro, Tohru Miyazaki, Kouji Mori, Noriko Uchiyama, Kenichi Iwai, Akihiro Ohashi, Hideto Hara, Sei Yoshida, Nobuo Cho
In order to increase the success rate for developing new Cdc7 inhibitors for cancer therapy, we explored a new chemotype which can comply with the previously-constructed pharmacophore model. Substitution of a pyridine ring of a serendipitously-identified Cdc7 inhibitor 2b with a 3-methylpyrazole resulted in a 4-fold increase in potency and acceptable kinase selectivity, leading to the identification of thieno[3,2-d]pyrimidin-4(3H)-one as an alternative scaffold. Structure-activity relationship (SAR) study revealed that incorporation of a substituted aminomethyl group into the 2-position improved kinase selectivity...
May 2, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28521412/microrna-335-and-its-target-rock1-synergistically-influence-tumor-progression-and-prognosis-in-osteosarcoma
#18
Yong Wang, Ningning Wang, Xiandong Zeng, Jie Sun, Guangbin Wang, Huimian Xu, Wei Zhao
MicroRNA (miR)-335 and Rho-associated serine-threonine protein kinase 1 (Rock1) is ectopically expressed in multiple malignant tumors including osteosarcoma. The present study aimed to clarify whether the combined ectopically expressed miR-335 and Rock1 was correlated with clinicopathological features and prognosis in patients with osteosarcoma. The expression of miR-335 and Rock1 in 91 osteosarcoma tissue samples and 47 noncancerous bone tissues were determined respectively by in situ hybridization and immunohistochemistry...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28487419/membrane-depolarization-activates-bk-channels-through-rock-mediated-%C3%AE-1-subunit-surface-trafficking-to-limit-vasoconstriction
#19
M Dennis Leo, Xue Zhai, Padmapriya Muralidharan, Korah P Kuruvilla, Simon Bulley, Frederick A Boop, Jonathan H Jaggar
Membrane depolarization of smooth muscle cells (myocytes) in the small arteries that regulate regional organ blood flow leads to vasoconstriction. Membrane depolarization also activates large-conductance calcium (Ca(2+))-activated potassium (BK) channels, which limits Ca(2+) channel activity that promotes vasoconstriction, thus leading to vasodilation. We showed that in human and rat arterial myocytes, membrane depolarization rapidly increased the cell surface abundance of auxiliary BK β1 subunits but not that of the pore-forming BKα channels...
May 9, 2017: Science Signaling
https://www.readbyqxmd.com/read/28484504/effect-of-qskl-on-mapk-and-rhoa-pathways-in-a-rat-model-of-heart-failure
#20
Kai Xia, Qiyan Wang, Chun Li, Zifan Zeng, Yong Wang, Wei Wang
Qishenkeli (QSKL) is one of the Chinese medicine formulae for treating heart failure and has been shown to have an antifibrotic effect. However, the mechanism of its therapeutic effects remains unclear. In this study, we aimed to explore whether QSKL could exert an antifibrotic effect by attenuating ras homolog family member A (RhoA) and mitogen activated protein kinase (MAPK) pathways. Rats were randomly divided into sham group, model group, QSKL group, and positive control group. Heart failure was induced by ligation of the left ventricle anterior descending artery...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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