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Liang Yue, Hai-Fan Yu, Zhan-Qing Yang, Xue-Chao Tian, Lian-Wen Zheng, Bin Guo
Although Egr2 is involved in regulating the folliculogenesis and ovulation, there is almost no data describing its physiological function in embryo implantation and decidualization. Here, we showed that Egr2 mRNA was distinctly accumulated in subluminal stromal cells around implanting blastocyst on day 5 of pregnancy as well as in estrogen-activated implantation uterus. Estrogen induced the expression of Egr2 in uterine epithelia. Elevated expression of Egr2 mRNA was also observed in the decidual cells. Silencing of Egr2 by specific siRNA weakened the proliferation of uterine stromal cells and reduced the expression of Ccnd1, Ccnd3, Cdk4, and Cdk6...
May 20, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
Ming-Zhao Gao, Hong-Bin Wang, Xiang-Ling Chen, Wen-Ting Cao, Li Fu, Yun Li, Hai-Tian Quan, Cheng-Ying Xie, Li-Guang Lou
BRAF and MEK inhibitors have shown remarkable clinical efficacy in BRAF-mutant melanoma; however, most patients develop resistance, which limits the clinical benefit of these agents. In this study, we found that the human melanoma cell clones, A375-DR and A375-TR, with acquired resistance to BRAF inhibitor dabrafenib and MEK inhibitor trametinib, were cross resistant to other MAPK pathway inhibitors. In these resistant cells, phosphorylation of ribosomal protein S6 (rpS6) but not phosphorylation of ERK or p90 ribosomal S6 kinase (RSK) were unable to be inhibited by MAPK pathway inhibitors...
May 18, 2018: Acta Pharmacologica Sinica
Diana I Sánchez, Bárbara González-Fernández, Irene Crespo, Beatriz San-Miguel, Marcelino Álvarez, Javier González-Gallego, María Jesús Tuñón
Disruption of circadian rhythms, which are regulated by the circadian clock machinery, plays an important role in different long-term diseases including hepatocellular carcinoma (HCC). Melatonin has been reported to alleviate promotion and progression of HCC, but the potential contribution of circadian clock modulation is unknown. We investigated the effects of melatonin in mice which received diethylnitrosamine (DEN) (35 mg/kg body weight i.p.) once a week for 8 weeks. Melatonin was given at 5 or 10 mg/kg/day i...
May 16, 2018: Journal of Pineal Research
Annika Jacobsen, Linda J W Bosch, Sanne R Martens-de Kemp, Beatriz Carvalho, Anke H Sillars-Hardebol, Richard J Dobson, Emanuele de Rinaldis, Gerrit A Meijer, Sanne Abeln, Jaap Heringa, Remond J A Fijneman, K Anton Feenstra
Hyperactivation of Wnt and Ras-MAPK signalling are common events in development of colorectal adenomas. Further progression from adenoma-to-carcinoma is frequently associated with 20q gain and overexpression of Aurora kinase A (AURKA). Interestingly, AURKA has been shown to further enhance Wnt and Ras-MAPK signalling. However, the molecular details of these interactions in driving colorectal carcinogenesis remain poorly understood. Here we first performed differential expression analysis (DEA) of AURKA knockdown in two colorectal cancer (CRC) cell lines with 20q gain and AURKA overexpression...
May 14, 2018: Scientific Reports
Xiaoxiao Gao, Li Han, Nan Ding, Yu Mu, Peipei Guan, Caijuan Hu, Xueshi Huang
Bafilomycin C1, which was isolated from Streptomyces albolongus in our previous work, exhibited strong cytotoxicity against several cancer cell lines. This study aimed to evaluate its antitumor effect on human hepatocellular cancer SMMC7721 cells and the underlying mechanism in vitro and in vivo. MTT assay revealed that bafilomycin C1 retarded SMMC7721 cell growth and proliferation. Western blot and real-time qPCR analysis revealed that bafilomycin C1 caused partial G0/G1 phase cell-cycle arrest, downregulated the expression of cyclin D3, cyclin E1, CDK2, CDK4, and CDK6 and upregulated the expression of p21...
May 11, 2018: Journal of Antibiotics
Longfei Yang, Huanran Liu, Min Long, Xi Wang, Fang Lin, Zhaowei Gao, Huizhong Zhang
Background: Targeted therapies have been proven as promising in the treatment of breast cancer and have improved survival and quality of life in advanced breast cancer. We previously identified a novel peptide SA12 which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 cells. Methods: The present study investigated the potential antitumor role of SA12 in breast cancer cell lines MDA-MB-231 and MCF-7 through Cell Counting Kit-8 assay and colony formation assay, and examined the cell cycle distribution using flow cytometry analysis...
2018: OncoTargets and Therapy
Mei Lv, Yi Wang, Wenmiao Wu, Shujun Yang, Huiling Zhu, Bei Hu, Ying Chen, Cong Shi, Yi Zhang, Qitian Mu, Guifang Ouyang
The long‑term survival rate in paediatric acute lymphoblastic leukaemia (ALL) exceeds 80%; however, the outcome of adult ALL remains to be poor. Glucocorticoids (GCs) are the preferred drugs in the traditional treatment of ALL patients. In the anti‑leukaemia molecular mechanisms of GCs, c‑Myc inhibition serves a critical role. In the present study, a c‑Myc inhibitor that increased the sensitivity to GCs in NALM6 cells of the B‑cell‑ALL cell line and CEM cells of the T‑cell‑ALL cell line was investigated...
April 27, 2018: Molecular Medicine Reports
Nirmala Jagadish, Rukhsar Fatima, Aditi Sharma, Sonika Devi, Vitusha Suri, Vikash Kumar, Anil Suri
SPAG9 is a novel tumor associated antigen, expressed in variety of malignancies. However, its role in ovarian cancer remains unexplored. SPAG9 expression was validated in ovarian cancer cells by real time PCR and Western blot. SPAG9 involvement in cell cycle, DNA damage, apoptosis, paclitaxel sensitivity and epithelial- mesenchymal transition (EMT) was investigated employing RNA interference approach. Combinatorial effect of SPAG9 ablation and paclitaxel treatment was evaluated in in vitro. Quantitative PCR and Western blot analysis revealed SPAG9 expression in A10, SKOV-3 and Caov3 compared to normal ovarian epithelial cells...
May 2018: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaogang Jing, Tianci Jiang, Lingling Dai, Xi Wang, Liuqun Jia, Huan Wang, Lin An, Meng Liu, Rui Zhang, Zhe Cheng
OBJECTIVES: This study aimed to investigate whether autophagy mediated cell proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) under hypoxia and to validate the underlying mechanism. METHODS: The rat model of chronic hypoxia-induced pulmonary vascular remodeling was established. Rat primary PASMCs were isolated and cultured in vitro in hypoxia or normoxia to explore the underlying mechanism. RESULTS: Hypoxia exposure for 21 days induced pulmonary vascular remodeling in rats, accompanied by enhanced proliferation and decreased apoptosis, as well as induced expression of autophagic marker LC3II in their lungs...
May 4, 2018: Experimental Cell Research
Yuxin Feng, Senhao Xiao, Yantao Chen, Hao Jiang, Na Liu, Cheng Luo, Shijie Chen, Hua Chen
Compound 1 bearing with benzo [cd]indol-2(1H)-one scaffold was identified as an effective BRD4 inhibitor through the AlphaScreen-based high-throughput screening and its high-resolution crystal structure with BRD4_BD1 protein. A series of 48 compounds were designed and synthesized by structural optimization on compound 1. All the compounds have been evaluated for their BRD4 inhibitory activities. The results showed that compounds 23, 24, 28 and 44 are the most potential ones with the IC50 values of 1.02 μM, 1...
April 28, 2018: European Journal of Medicinal Chemistry
Nicolas Caron, Emmanuelle C Genin, Quentin Marlier, Sébastien Verteneuil, Pierre Beukelaers, Laurence Morel, Miaofen G Hu, Philip W Hinds, Laurent Nguyen, Renaud Vandenbosch, Brigitte Malgrange
Neural stem cells give rise to granule dentate neurons throughout life in the hippocampus. Upon activation, these stem cells generate fast proliferating progenitors that complete several rounds of divisions before differentiating into neurons. Although the mechanisms regulating the activation of stem cells have been intensively studied, little attention has been given so far to the intrinsic machinery allowing the expansion of the progenitor pool. The cell cycle protein Cdk6 positively regulates the proliferation of hippocampal progenitors, but the mechanism involved remains elusive...
May 4, 2018: Cellular and Molecular Life Sciences: CMLS
Jingxiao Zhang, Lilei Zhang, Yangcheng Xu, Shanshan Jiang, Yueyue Shao
Flavonoids, a class of natural compounds with variable phenolic structures, have been found to possess anti-cancer activities by modulating different enzymes and receptors like CDK6. To understand the binding behavior of flavonoids that inhibit the active CDK6, molecular dynamics (MD) simulations were performed on six inhibitors, chrysin (M01), fisetin (M03), galangin (M04), genistein (M05), quercetin (M06) and kaempferol (M07), complexed with CDK6/cyclin D. For all six flavonoids, the 3'-OH and 4'-OH of B-ring were found to be favorable for hydrogen bond formation, but the 3-OH on the C-ring and 5-OH on the A-ring were unfavorable, which were confirmed by the MD simulation results of the test molecule, 3', 4', 7-trihydroxyflavone (M15)...
2018: PloS One
Dan Xu, Dong Liang, Yubing Guo, Yeqing Sun
Exposure to pesticides results in DNA damage and genomic instability. We previously predicted that endosulfan might be associated with leukemia, but the role of endosulfan in leukemia cells has been unexplored. The aim of this study is to elucidate molecular mechanism of endosulfan-induced DNA damage response in human leukemia cells. We performed endosulfan exposure experiments in K562 cells with varying concentrations of endosulfan for 48 h and found that endosulfan lowered cell viability in a dose-dependent manner...
April 25, 2018: Environmental Pollution
Antoine Buetti-Dinh, Ran Friedman
BACKGROUND: Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies. RESULTS: Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3...
April 24, 2018: BMC Bioinformatics
Chaoqi Ren, Mengmeng Yu, Yao Zhang, Minghui Fan, Fangfang Chang, Lixiao Xing, Yongzhen Liu, Yongqiang Wang, Xiaole Qi, Changjun Liu, Yanping Zhang, Hongyu Cui, Kai Li, Li Gao, Qing Pan, Xiaomei Wang, Yulong Gao
Avian leukosis virus subgroup J (ALV-J), a highly oncogenic retrovirus, causes leukemia-like proliferative diseases in chickens. microRNAs post-transcriptionally suppress targets and are involved in the development of various tumors. We previously showed that miR-221 is upregulated in ALV-J-induced tumors. In this study, we analyzed the possible function of miR-221 in ALV-J tumorigenesis. The target validation system showed that CDKN1B is a target of miR-221 and is downregulated in ALV-J infection. As CDKN1B arrests the cell cycle and regulates its progression, we analyzed the proliferation of ALV-J-infected DF-1 cells...
April 23, 2018: Virology
Azadeh Andisheh-Tadbir, Mohammad Javad Ashraf, Naghmeh Jeiroodi
Background: CDK6 is the key factor in regulation of the cell cycle and essential for passage into the G1 phase. It also plays an important role in the development of various tumors. In this cross-sectional study expression of the CDK6 protein in oral squamous cell carcinoma (OSCC) and healthy oral mucosa of controls was assessed to determine relations with malignant transformation and clinicopathologic factors. Method: A total of 60 samples, 45 from OSCCs and 15 from healthy tissue, underwent immunohistochemistry for CDK6...
April 25, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
Enrique Rozengurt, James Sinnett-Smith, Guido Eibl
Pancreatic ductal adenocarcinoma (PDAC) is generally a fatal disease with no efficacious treatment modalities. Elucidation of signaling mechanisms that will lead to the identification of novel targets for therapy and chemoprevention is urgently needed. Here, we review the role of Yes-associated protein (YAP) and WW-domain-containing Transcriptional co-Activator with a PDZ-binding motif (TAZ) in the development of PDAC. These oncogenic proteins are at the center of a signaling network that involves multiple upstream signals and downstream YAP-regulated genes...
2018: Signal Transduction and Targeted Therapy
Guangwen Li, Qingfeng Ma, Rongliang Wang, Zhibin Fan, Zhen Tao, Ping Liu, Haiping Zhao, Yumin Luo
Our previous study demonstrated that microRNA-424 (miR-424) protected against experimental stroke through inhibition of microglial proliferation and activation by targeting cell cycle proteins. The purpose of this study was to further explore the clinical significance of miR-424 in peripheral immune cells of patients with acute ischemic stroke (AIS). Blood samples were collected from 40 patients within 6 hours of symptom onset and 27 control subjects. MiR-424 levels in lymphocytes, neutrophils and plasma were determined by quantitative realtime-PCR...
April 2018: Aging and Disease
Ivana Jovčevska
The most aggressive brain malignancy, glioblastoma, accounts for 60-70% of all gliomas and is uniformly fatal. According to the molecular signature, glioblastoma is divided into four subtypes (proneural, neural, classical, and mesenchymal), each with its own genetic background. The Cancer Genome Atlas project provides information about the most common genetic changes in glioblastoma. They involve mutations in TP53, TERT, and PTEN, and amplifications in EFGR, PDGFRA, CDK4, CDK6, MDM2, and MDM4. Recently, epigenetics was used to demonstrate the oncogenic roles of miR-124, miR-137, and miR-128...
April 18, 2018: Critical Reviews in Clinical Laboratory Sciences
Demeng Chen, Zhiqiang Zhao, Zixin Huang, Du-Chu Chen, Xin-Xing Zhu, Yi-Ze Wang, Ya-Wei Yan, Shaojun Tang, Subha Madhavan, Weiyi Ni, Zhan-Peng Huang, Wen Li, Weidong Ji, Huangxuan Shen, Shuibin Lin, Yi-Zhou Jiang
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients...
2018: Bone Research
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