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Wei Huang, Yuliang Feng, Jialiang Liang, Hao Yu, Cheng Wang, Boyu Wang, Mingyang Wang, Lin Jiang, Wei Meng, Wenfeng Cai, Mario Medvedovic, Jenny Chen, Christian Paul, W Sean Davidson, Sakthivel Sadayappan, Peter J Stambrook, Xi-Yong Yu, Yigang Wang
The goal of replenishing the cardiomyocyte (CM) population using regenerative therapies following myocardial infarction (MI) is hampered by the limited regeneration capacity of adult CMs, partially due to their withdrawal from the cell cycle. Here, we show that microRNA-128 (miR-128) is upregulated in CMs during the postnatal switch from proliferation to terminal differentiation. In neonatal mice, cardiac-specific overexpression of miR-128 impairs CM proliferation and cardiac function, while miR-128 deletion extends proliferation of postnatal CMs by enhancing expression of the chromatin modifier SUZ12, which suppresses p27 (cyclin-dependent kinase inhibitor) expression and activates the positive cell cycle regulators Cyclin E and CDK2...
February 16, 2018: Nature Communications
Christian Arquint, Fabien Cubizolles, Agathe Morand, Alexander Schmidt, Erich A Nigg
Deregulation of centriole duplication has been implicated in cancer and primary microcephaly. Accordingly, it is important to understand how key centriole duplication factors are regulated. E3 ubiquitin ligases have been implicated in controlling the levels of several duplication factors, including PLK4, STIL and SAS-6, but the precise mechanisms ensuring centriole homeostasis remain to be fully understood. Here, we have combined proteomics approaches with the use of MLN4924, a generic inhibitor of SCF E3 ubiquitin ligases, to monitor changes in the cellular abundance of centriole duplication factors...
February 2018: Open Biology
Hongshan Yan, Kunxiu Song, Guohui Zhang
Wound healing is a fundamental biological process to restore skin integrity. The role of microRNAs (miRNAs) during this process remains elusive. Thus, our study aimed to investigate the biological functions and its molecular mechanisms of miR-17-3p in cutaneous wound healing. Human keratinocyte cell line HaCaT was transfected with miR-17-3p mimic, antisense oligonucleotides (ASO)-miR-17-3p and corresponding controls respectively. After transfection, MTT, flow cytometry, qRT-PCR and western blot were performed to analyze cell viability, colony-formation and cell cycle...
September 1, 2017: Die Pharmazie
Wenzhi Li, Zhe Sun, Chen Chen, Lin Wang, Zhimin Geng, Jie Tao
Accumulating evidence indicates that sirtuin7 (SIRT7) plays an oncogenic role in the main types of liver cancer, hepatocellular carcinoma (HCC). Nevertheless, the clinical significance of SIRT7 and its role in cholangiocarcinoma (CCA) is largely undiscovered. Here, we found that SIRT7 displayed higher expression in CCA tissues compared to intrahepatic normal bile duct and surrounding liver tissues based on The Cancer Genome Atlas (TCGA) data. Our data further confirmed that SIRT7 was overexpressed in CCA patient tissues and cell lines...
February 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Shi-Lung Lin, Shao-Yao Ying
Today's researchers generating induced pluripotent stem cells (iPS cells or iPSCs) usually consider their pluripotency rather than potential tumorigenicity. Oncogenic factors such as c-Myc and Klf4 are frequently used to boost the survival and proliferative rates of iPSCs, creating an inevitable problem of tumorigenicity that hinders the therapeutic usefulness of these iPSCs. To prevent stem cell tumorigenicity, we have examined mechanisms by which the cell cycle genes are regulated in embryonic stem cells (ESCs)...
2018: Methods in Molecular Biology
Caroline M Robb, Smit Kour, Jacob I Contreras, Ekta Agarwal, Carter J Barger, Sandeep Rana, Yogesh Sonawane, Beth K Neilsen, Margaret Taylor, Smitha Kizhake, Rhishikesh N Thakare, Sanjib Chowdhury, Jing Wang, Jennifer D Black, Michael A Hollingsworth, Michael G Brattain, Amarnath Natarajan
Colorectal cancer (CRC) remains one of the leading causes of cancer related deaths in the United States. Currently, there are limited therapeutic options for patients suffering from CRC, none of which focus on the cell signaling mechanisms controlled by the popular kinase family, cyclin dependent kinases (CDKs). Here we evaluate a Pfizer developed compound, CP668863, that inhibits cyclin-dependent kinase 5 (CDK5) in neurodegenerative disorders. CDK5 has been implicated in a number of cancers, most recently as an oncogene in colorectal cancers...
January 12, 2018: Oncotarget
Huan Liu, Qin Luo, Hengmin Cui, Huidan Deng, Ping Kuang, Yujiao Lu, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, Ling Zhao
In this study, experimental pathology, flow cytometry (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), and western blot (WB) were used to evaluate the effects of sodium fluoride (NaF) on hepatocellular cell cycle progression in mice. A total of 240 ICR mice were divided equally into four groups; the experimental groups received 12, 24, or 48 mg/kg NaF intragastrically for 42 days, while the control group received distilled water. Doses of NaF above 12 mg/kg increased the percentage of cells in S phase (S-phase arrest), reduced percentages of cells in G0/G1 or G2/M phase, and activated the ATM-p53-p21 and ATR-Chk1-Cdc25A pathways...
January 12, 2018: Oncotarget
Kamila Kitowska, Agnieszka Kowalska, Magdalena Mieszkowska, Dominika Piasecka, Andrzej C Skladanowski, Hanna M Romanska, Rafal Sadej
Breast cancer (BCa) is the most common cancer affecting women worldwide. Overexpression of human epidermal growth factor receptor 2 (HER2) occurs in ~20-25% of invasive ductal breast carcinomas and is associated with the more aggressive phenotype. Herceptin, a humanized antibody against HER2, is a standard therapy in HER2-overexpressing cases. Approximately one-third of patients relapse despite treatment. Therefore numerous studies have investigated the molecular mechanisms associated with Herceptin resistance...
February 2018: Oncology Letters
Shalini Nath, Chhabinath Mandal, Uttara Chatterjee, Chitra Mandal
Modulation of sialylation by sialyltransferases and sialidases plays essential role in carcinogenesis. There are few reports on sialyltransferase, however, the contribution of cytosolic sialidase (Neu2) remains unexplored in pancreatic ductal adenocarcinoma (PDAC). We observed lower expression of Neu2 in different PDAC cells, patient tissues, and a significant strong association with clinicopathological characteristics. Neu2 overexpression guided drug-resistant MIAPaCa2 and AsPC1 cells toward apoptosis as evidenced by decreased Bcl2/Bax ratio, activation of caspase-3/caspase-6/caspase-8, PARP reduction, reduced CDK2/CDK4/CDK6, and cyclin-B1/cyclin-E with unaffected caspase-9...
February 12, 2018: Cell Death & Disease
Masanori Kawakami, Lisa Maria Mustachio, Lin Zheng, Yulong Chen, Jaime Rodriguez-Canales, Barbara Mino, Jonathan M Kurie, Jason Roszik, Pamela Andrea Villalobos, Kelsie L Thu, Jennifer Silvester, David W Cescon, Ignacio I Wistuba, Tak W Mak, Xi Liu, Ethan Dmitrovsky
Polo-like kinase 4 (PLK4) is a serine/threonine kinase regulating centriole duplication. CFI-400945 is a highly selective PLK4 inhibitor that deregulates centriole duplication, causing mitotic defects and death of aneuploid cancers. Prior work was substantially extended by showing CFI-400945 causes polyploidy, growth inhibition, and apoptotic death of murine and human lung cancer cells, despite expression of mutated KRAS or p53. Analysis of DNA content by propidium iodide (PI) staining revealed cells with >4N DNA content (polyploidy) markedly increased after CFI-400945 treatment...
February 6, 2018: Proceedings of the National Academy of Sciences of the United States of America
Lina Xu, Lina Gu, Xufeng Tao, Youwei Xu, Yan Qi, Lianhong Yin, Xu Han, Jinyong Peng
BACKGROUND: Development of novel candidates to promote liver regeneration is critical important after partial hepatectomy (PH). Dioscin, a natural product, shows potent effect on liver protection in our previous works. PURPOSE: This work aimed to investigate the effect and underlying mechanisms of dioscin on liver regeneration. METHODS: The promoting proliferation effects of dioscin on mouse hepatocytem AML12 cells, rat primary hepatocytes, rats and mice after 70% PH were evaluated...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Kohei Nukina, Akiyo Hayashi, Yasushi Shiomi, Kaoru Sugasawa, Motoaki Ohtsubo, Hideo Nishitani
CRL4Cdt2 ubiquitin ligase plays an important role maintaining genome integrity during the cell cycle. A recent report suggested that Cdk1 negatively regulates CRL4Cdt2 activity through phosphorylation of its receptor, Cdt2, but the involvement of phosphorylation remains unclear. To address this, we mutated all CDK consensus phosphorylation sites located in the C-terminal half region of Cdt2 (Cdt2-18A) and examined the effect on substrate degradation. We show that both cyclinA/Cdk2 and cyclinB/Cdk1 phosphorylated Cdt2 in vitro and that phosphorylation was reduced by the 18A mutation both in vitro and in vivo...
February 9, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Feifei Wang, Songli Zhu, Laura A Fisher, Weidong Wang, Gregory G Oakley, Chunling Li, Aimin Peng
The specific function of PP2A, a major serine/threonine phosphatase, is mediated by regulatory targeting subunits, such as members of the B55 family. Although implicated in cell division and other pathways, the specific substrates and functions of B55 targeting subunits are largely undefined. In this study we identified over 100 binding proteins of B55α and B55β in Xenopus egg extracts that are involved in metabolism, mitochondria function, molecular trafficking, cell division, cytoskeleton, DNA replication, DNA repair, and cell signaling...
February 8, 2018: Scientific Reports
Imran Khan, Ashutosh Bahuguna, Monika Bhardwaj, Tejinder Pal Khaket, Sun Chul Kang
Carvacrol is a monoterpenoid flavonoid found abundantly in thyme plants. Its physiochemical instability and partial solubility in water is the principal limitation for its industrial use. Hence, we made a carvacrol nanoemulsion (CANE) using ultrasonication method and characterized it by dynamic light scattering (DLS) technique which revealed a negative surface charge (-29.89 mV) with 99.1 nm average droplet size. CANE effectively induced apoptosis in doxorubicin-resistant A549 lung carcinoma cells (A549 DR ) evident by the elevated expression of apoptotic proteins such as Bax, Cytochrome C, and Cleaved caspase 3 and 9...
February 6, 2018: Artificial Cells, Nanomedicine, and Biotechnology
Chao-Jie Wang, Li-Juan Wang, Ding Zhao
OBJECTIVE: To explore the effect of PKA gene on acute T lymphocyte leukemia cells in children and its mechanism. METHODS: Jurkat and Sup-T1 cells were divided into 2 group: control group (Jurkat and Sup-T1 cells treated with non-specific siRNA) and transfected group (Jurkat and Sup-T1 cells transfected with PKA siRNA). The effects of down-regulating the expression of PKA gene on the viability, proliferotion, migration and cell cycle distribution of Jurkat and Sup-T1 cells in 2 groups were analyzed by CCK-8 assay, transwell experiment, cell colony-formation test and flow cytometry; the cyclin-related protein levels after transfection with PKA siRNA were detected by Western blot...
February 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Yun-Soo Seo, Ok-Hwa Kang, Ryong Kong, Tian Zhou, Sang-A Kim, Shiyong Ryu, Hak-Ryul Kim, Dong-Yeul Kwon
Polygalacin D (PGD) is a bioactive compound isolated from Platycodon grandiflorum (Jacq.) and it has a similar structure to platycodin D, which is a well known anticancer agent. In the present study, we investigated the anti-proliferative effects of PGD using NSCLC cell lines. We evaluated the effects of PGD on proliferation, apoptosis and cell cycle arrest in A549 and H460 cells. PGD significantly induced apoptosis and nuclear condensation in both cell lines. Furthermore, PGD upregulated the cleavage of apoptotic proteins such as caspase-3, -9 and PARP...
January 23, 2018: Oncology Reports
Wanlin Liu, Zhenqun Zhao, Yuyan Na, Chenyang Meng, Jianzhong Wang, Rui Bai
Apoptosis of osteoblasts, triggered by prolonged or excessive use of glucocorticoids (GCs), has been identified as a dominant contributor to the development of osteoporosis and osteonecrosis. However, the molecular mechanisms underlying GC‑induced apoptosis are multifaceted and remain to be fully elucidated. The present study aimed to explore the correlation between dexamethasone (DEX)‑induced reactive oxygen species (ROS), autophagy and apoptosis in MC3T3‑E1 osteoblast‑like cells. Cell viability was assessed using a Cell Counting Kit‑8 assay, and flow cytometry was performed to assess cellular apoptosis, cell cycle and ROS production...
January 23, 2018: International Journal of Molecular Medicine
Isnatin Miladiyah, Jumina Jumina, Sofia Mubarika Haryana, Mustofa Mustofa
Background: Xanthone derivatives have a wide range of pharmacological activities, such as those involving antibacterial, antiviral, antimalarial, anthelmintic, anti-inflammatory, antiprotozoal, and anticancer properties. Among these, we investigated the anticancer properties of xanthone. This research aimed to analyze the biological activity of ten novel xanthone derivatives, to investigate the most contributing-descriptors for their cytotoxic activities, and to examine the possible mechanism of actions of xanthone compound through molecular docking...
2018: Drug Design, Development and Therapy
Feng Shuai, Bo Wang, Shuxiao Dong
miR-522-3p is known to degrade bloom syndrome protein (BLM) and enhance expression of other proto-oncogenes leading totumorigenesis. This study aimed to investigate the molecular mechanisms of miR-522-3p in human colorectal cancer (CRC) cells. Expressions of miR-522-3p in CRC and adjacent tissues, as well as in normal human colon epithelial cell line (FHC) and five CRC cell lines were detected. Human CRC cell lines, HCT-116 and HT29, were transfected with miR-522-3p mimic, inhibitor or scrambled controls. Then, cell viability, apoptosis, cell-cycle progression, and the expressions of c-myc, cyclin E, CDK2, and BLM were respectively assessed...
January 31, 2018: Oncology Research
Ting Yan, Gaosheng Hu, Anhua Wang, Xianduo Sun, Xiangyong Yu, Jingming Jia
Paris saponinVII (PSVII) is a steroidal saponin isolated from the roots and rhizomes of Trillium tschonoskii Maxim. We found that PSVII could inhibit the growth of adriamycin-resistant human leukemia cells (K562/ADR) in a dose-dependent manner. Furthermore, the molecular mechanism underlying the cytotoxicity and downregulation of P-glycoprotein (P-gp) expression by PSVII was clarified. PSVII significantly suppressed cell proliferation by cell cycle arrest in the G0/G1 phase, which was associated with an obvious decrease in cyclin B1/D1 and CDK2/4/6 protein expression...
January 29, 2018: Phytotherapy Research: PTR
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