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Chieh-Yuan Cheng, Chung-Ji Liu, Yu-Chuen Huang, Shu-Hua Wu, Hsu-Wei Fang, Yu-Jen Chen
BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA knockdown experiments were used to assess cell viability, morphology, cell cycle progression, radiation survival, and expression of regulatory proteins in vitro ...
April 20, 2018: Oncotarget
Soumya Chaurasia, Christian F Lehner
Sister kinetochores are connected to the same spindle pole during meiosis I and to opposite poles during meiosis II. The molecular mechanisms controlling the distinct behavior of sister kinetochores during the two meiotic divisions are poorly understood. To study kinetochore behavior during meiosis, we have optimized time lapse imaging with Drosophila spermatocytes, enabling kinetochore tracking with high temporal and spatial resolution through both meiotic divisions. The correct bipolar orientation of chromosomes within the spindle proceeds rapidly during both divisions...
May 7, 2018: PLoS Genetics
Dong-Yue Wen, Peng Lin, Yu-Yan Pang, Gang Chen, Yun He, Yi-Wu Dang, Hong Yang
BACKGROUND Long non-coding RNAs (lncRNAs) have a role in physiological and pathological processes, including cancer. The aim of this study was to investigate the expression of the long intergenic non-protein coding RNA 665 (LINC00665) gene and the cell cycle in hepatocellular carcinoma (HCC) using database analysis including The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and quantitative real-time polymerase chain reaction (qPCR). MATERIAL AND METHODS Expression levels of LINC00665 were compared between human tissue samples of HCC and adjacent normal liver, clinicopathological correlations were made using TCGA and the GEO, and qPCR was performed to validate the findings...
May 5, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Xiaoye Liu, Feifei Zhang, Yaping Zhang, Xie Li, Chiqi Chen, Meiyi Zhou, Zhuo Yu, Yunxia Liu, Yuzheng Zhao, Xiaoxin Hao, Yabin Tang, Liang Zhu, Ligen Liu, Li Xie, Hao Gu, Hongfang Shao, Fangzhen Xia, Chunrong Yin, Minfang Tao, Jingjing Xie, Cheng Cheng Zhang, Yi Yang, Haipeng Sun, Guo-Qiang Chen, Junke Zheng
In addition to acting as building blocks for biosynthesis, amino acids might serve as signaling regulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we could monitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20...
May 1, 2018: Cell Reports
Yun Yeon Park, Ju-Hyun Ahn, Min-Guk Cho, Jae-Ho Lee
ATP depletion inhibits cell cycle progression, especially during the G1 phase and the G2 to M transition. However, the effect of ATP depletion on mitotic progression remains unclear. We observed that the reduction of ATP after prometaphase by simultaneous treatment with 2-deoxyglucose and NaN3 did not arrest mitotic progression. Interestingly, ATP depletion during nocodazole-induced prometaphase arrest resulted in mitotic slippage, as indicated by a reduction in mitotic cells, APC/C-dependent degradation of cyclin B1, increased cell attachment, and increased nuclear membrane reassembly...
April 27, 2018: Experimental & Molecular Medicine
Guang-Yu Wang, Ling Li, Bo Liu, Xiao Han, Chun-Hua Wang, Ji-Wen Wang
Purpose: This study aimed to explore significant genes and pathways involved in the pathogenesis of supratentorial primitive neuroectodermal tumor (sPNET). Materials and methods: Gene expression profile of GSE14295 was downloaded from publicly available Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened out in primary sPNET samples compared with normal fetal and adult brain reference samples (sPNET vs fetal brain and sPNET vs adult brain)...
2018: OncoTargets and Therapy
Guang-Jie Jiang, Yan-Hua Chen, Wei Guo, Hang Zhang, Lin Zou
OBJECTIVE: To explore the key genes in T-cell acute lymphoblastic leukemia (T-ALL) using bioinformatics method to better understand the pathogenic mechanisms of T-ALL. METHODS: The gene expression profiles of GSE14317 were obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) in T-ALL were analyzed using R package Limma. The online analysis tool DAVID was used to perform the functional and pathway enrichment analysis. The protein-protein interaction network was constructed by STRING and visualized by Cytoscape...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Zehua Wang, Bo Yang, Min Zhang, Weiwei Guo, Zhiyuan Wu, Yue Wang, Lin Jia, Song Li, Wen Xie, Da Yang
We characterized the epigenetic landscape of genes encoding long noncoding RNAs (lncRNAs) across 6,475 tumors and 455 cancer cell lines. In stark contrast to the CpG island hypermethylation phenotype in cancer, we observed a recurrent hypomethylation of 1,006 lncRNA genes in cancer, including EPIC1 (epigenetically-induced lncRNA1). Overexpression of EPIC1 is associated with poor prognosis in luminal B breast cancer patients and enhances tumor growth in vitro and in vivo. Mechanistically, EPIC1 promotes cell-cycle progression by interacting with MYC through EPIC1's 129-283 nt region...
March 31, 2018: Cancer Cell
Wan-Ting Liu, Yang Wang, Jing Zhang, Fei Ye, Xiao-Hui Huang, Bin Li, Qing-Yu He
Lung adenocarcinoma (LAC) is the most lethal cancer and the leading cause of cancer-related death worldwide. The identification of meaningful clusters of co-expressed genes or representative biomarkers may help improve the accuracy of LAC diagnoses. Public databases, such as the Gene Expression Omnibus (GEO), provide rich resources of valuable information for clinics, however, the integration of multiple microarray datasets from various platforms and institutes remained a challenge. To determine potential indicators of LAC, we performed genome-wide relative significance (GWRS), genome-wide global significance (GWGS) and support vector machine (SVM) analyses progressively to identify robust gene biomarker signatures from 5 different microarray datasets that included 330 samples...
March 30, 2018: Cancer Letters
Rahul Brahma, Sanathoi Gurumayum, Leimarembi Devi Naorem, Mathavan Muthaiyan, Jeyakodi Gopal, Amouda Venkatesan
Zika virus (ZIKV), a single-strand RNA flavivirus, is transmitted primarily through Aedes aegypti. The recent outbreaks in America and unexpected association between ZIKV infection and birth defects have triggered the global attention. This vouches to understand the molecular mechanisms of ZIKV infection to develop effective drug therapy. A systems-level understanding of biological process affected by ZIKV infection in fetal brain sample led us to identify the candidate genes for pharmaceutical intervention and potential biomarkers for diagnosis...
April 2, 2018: Viral Immunology
Xiuting Liu, Wei Zhou, Xin Zhang, Yang Ding, Qianming Du, Rong Hu
Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells...
April 1, 2018: International Journal of Cancer. Journal International du Cancer
Fei Wu, Yun Lin, Peng Cui, Hongyun Li, Lechao Zhang, Zeqiang Sun, Shengliang Huang, Shun Li, Shiming Huang, Qingli Zhao, Qingyong Liu
PURPOSE: At least to date, no effective treatment for advanced castration-resistant prostate cancer (CRPC) has been established. Recent studies indicated that cell division cycle 20 homolog (Cdc20) overexpression is associated with poor prognosis in patients with castration-resistant prostate cancer. However, the mechanism of Cdc20 in the development of docetaxel resistance in CRPC remains elusive. METHODS: In this study, the transcription of Cdc20 was confirmed in three independent CRPC cell lines derived from different tissues, including LNCaP, PC3, and DU145...
March 31, 2018: Cancer Chemotherapy and Pharmacology
Ling Shih Quek, Nicolas Grasset, Joanita Binte Jasmen, Kim S Robinson, Sophie Bellanger
Cdc20 and Cdh1 activate the anaphase-promoting complex/cyclosome, a master cell cycle regulator. Although cell cycle modifications occur during differentiation of stem cells, a role for the anaphase-promoting complex/cyclosome on stem cell fate has not been established in embryonic or adult human tissues. We found that differentiated human primary keratinocytes from the skin express extremely low levels of Cdc20 compared with human primary keratinocyte stem cells (holoclones). In agreement with this, staining of human skin biopsies showed that Cdc20 is expressed in occasional cells from the basal and epibasal layers of the epidermis and is absent from the differentiated layers...
March 9, 2018: Journal of Investigative Dermatology
Wenhao Guo, Kunhong Zhong, Heng Wei, Chunlai Nie, Zhu Yuan
Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) play a critical role in the development of human cancers including pancreatic cancer. Long non-coding RNA SPRY4-IT1 (sprouty4-intron transcript 1) has been reported to play an oncogenic role in various types of human carcinomas. However, the role of SPRY4-IT1 in pancreatic cancer is unclear. The objective of this study was to determine the function of SPRY4-IT1 on proliferation and invasion in pancreatic cancer. In the current study, we dissected the function and mechanism of SPRY4-IT1 by multiple approaches including Real-time RT-PCR, Western blotting analysis, MTT assay, Wound healing assay, Transwell assay, and transfection...
2018: PloS One
Nam Nhut Phan, Chih-Yang Wang, Kuan-Lun Li, Chien-Fu Chen, Chung-Chieh Chiao, Han-Gang Yu, Pung-Ling Huang, Yen-Chang Lin
Breast cancer is a dangerous disease that results in high mortality rates for cancer patients. Many methods have been developed for the treatment and prevention of this disease. Determining the expression patterns of certain target genes in specific subtypes of breast cancer is important for developing new therapies for breast cancer. In the present study, we performed a holistic approach to screening the mRNA expression of six members of the cell division cycle-associated gene family (CDCA) with a focus on breast cancer using the Oncomine and The Cancer Cell Line Encyclopedia (CCLE) databases...
January 23, 2018: Oncotarget
Chunguang Li, Liangtao Luo, Sheng Wei, Xiongbiao Wang
Invasive ductal carcinoma (IDC) is a common histological type of breast cancer. The aim of this study was to identify the potential crucial genes associated with IDC and to provide valid biological information for further investigations. The gene expression profiles of GSE10780 which contained 42 histologically normal breast tissues and 143 IDC tissues were downloaded from the GEO database. Functional and pathway enrichment analysis of differentially expressed genes (DEGs) were performed and protein-protein interaction (PPI) network was analyzed using Cytoscape...
January 23, 2018: Oncotarget
Danielle Sitry-Shevah, Sharon Kaisari, Adar Teichner, Shirly Miniowitz-Shemtov, Avram Hershko
The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of MCC. Previous studies indicated that the dissociation of APC/C-bound MCC requires ubiquitylation and suggested that the target of ubiquitylation is the Cdc20 component of MCC...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
Hoi Tang Ma, Randy Y C Poon
The spindle assembly checkpoint (SAC) prevents premature segregation of chromosomes during mitosis. This process requires structural remodeling of MAD2 from O-MAD2 to C-MAD2 conformation. After the checkpoint is satisfied, C-MAD2 is reverted to O-MAD2 to allow anaphase-promoting complex/cyclosome (APC/C) to trigger anaphase. Recently, the AAA+ -ATPase TRIP13 was shown to act in concert with p31comet to catalyze C- to O-MAD2. Paradoxically, although C-MAD2 is present in TRIP13-deficient cells, the SAC cannot be activated...
February 6, 2018: Cell Reports
Yuping Han, Xuefei Jin, Hui Zhou, Bin Liu
The aim of the present study was to further investigate the molecular mechanisms of bladder cancer. The microarray data GSE52519 were downloaded from Gene Expression Omnibus, comprising 9 bladder cancer and 3 normal bladder tissue samples. Differentially expressed genes (DEGs) were identified using Limma package analysis. Subsequently, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Reactome pathway enrichment analyses were performed for down- and upregulated DEGs. Transcription factors and genes associated with cancer from DEGs were identified...
January 2018: Oncology Letters
Charlotte Trussart, Céline Pirlot, Emmanuel Di Valentin, Jacques Piette, Yvette Habraken
Overexpression of the ubiquitous type II melanoma antigen-D2 (MAGED2) in numerous types of cancer suggests that this protein contributes to carcinogenesis, a well-documented characteristic of other MAGE proteins. Modification of MAGED2 intracellular localization during cell cycle phases and following treatment with camptothecin (CPT) and phosphorylation by ATM/ATR following ionizing irradiation led us to investigate the molecular functions of MAGED2 in the cellular response to DNA damage. Cell cycle regulators, cell cycle progression, and bromodeoxyuridine (BrdU) incorporation were compared between MAGED2-sufficient and -depleted U2OS cells following exposure to CPT...
February 1, 2018: Biochemical Pharmacology
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