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Daniel C Anacker, Heather L Aloor, Caitlin N Shepard, Gina M Lenzi, Bryan A Johnson, Baek Kim, Cary A Moody
Productive replication of human papillomaviruses (HPV) is restricted to the uppermost layers of the differentiating epithelia. How HPV ensures an adequate supply of cellular substrates for viral DNA synthesis in a differentiating environment is unclear. Here, we demonstrate that HPV31 positive cells exhibit increased dNTP pools and levels of RRM2, a component of the ribonucleotide reductase (RNR) complex, which is required for de novo synthesis of dNTPs. RRM2 depletion blocks productive replication, suggesting RRM2 provides dNTPs for viral DNA synthesis in differentiating cells...
October 17, 2016: Virology
Pierre-Damien Denechaud, Isabel C Lopez-Mejia, Lluis Fajas
No abstract text is available yet for this article.
October 2016: Médecine Sciences: M/S
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
October 14, 2016: Cell Death and Differentiation
Haojie Wu, Weihua Li, Minghui Zhang, Shutao Zhu, Dengfeng Zhang, Xiao Wang
OBJECTIVES: Osteosarcoma (OsC) is the most common primary bone malignant tumor with lower incidence and high degree of malignancy, but the exact mechanism remains unknown. More evidence demonstrated microRNAs (miRNAs) could contribute to tumor progression. In this study, we investigated the expression and functions of miR-320 in OsC cells. MATERIALS AND METHODS: miR-320 expression levels in several human OsC cell lines and human normal osteoblastic cell line were tested by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR)...
October 2016: Journal of Cancer Research and Therapeutics
Shifeng Su, Xiaoyu Chen, Jiang Geng, John T Minges, Gail Grossman, Elizabeth M Wilson
Melanoma antigen-A11 (MAGE-A11) is a proto-oncogene involved in androgen receptor signaling and androgen-dependent cell growth. In this report we provide evidence that MAGE-A11 interacts with Skp2 (S phase kinase-associated protein), the substrate recognition protein of the Skp1-Cullin1-F-box E3 ubiquitin ligase, and with Skp2 binding protein, cyclin A. A similar cyclin A binding motif in MAGE-A11 and Skp2A was consistent with a competitive relationship between MAGE-A11 and Skp2 in binding cyclin A. Skp2 inhibited MAGE-A11 interaction with cyclin A...
October 6, 2016: Molecular and Cellular Endocrinology
Jian-Li Gao, Yan-Mei Shui, Wei Jiang, En-Yi Huang, Qi-Yang Shou, Xin Ji, Bai-Cheng He, Gui-Yuan Lv, Tong-Chuan He
Hypoxic in the tumor mass is leading to the myeloproliferative-like disease (leukemoid reaction) and anemia of body, which characterized by strong extensive extramedullary hematopoiesis (EMH) in spleen. As the key transcription factor of hypoxia, hypoxia-inducible factor-1 (HIF-1) activates the expression of genes essential for EMH processes including enhanced blood cell production and angiogenesis. We found ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, inhibited growth of breast cancer both in vivo and in vitro...
September 30, 2016: Oncotarget
Clotilde Costa, Mirentxu Santos, Mónica Martínez-Fernández, Corina Lorz, Sara Lázaro, Jesús M Paramio
E2F/RB activity is altered in most human tumors. The retinoblastoma family of proteins plays a key role in regulating the progression of the cell cycle from the G1 to S phases. This is achieved through negative regulation of E2F transcription factors, important positive regulators of cell cycle entry. E2F family members are divided into two groups: activators (E2F1-E2F3a) and repressors (E2F3b-E2F8). E2F4 accounts for a large part of the E2F activity and is a main E2F repressor member in vivo. Perturbations in the balance from quiescence towards proliferation contribute to increased mitotic gene expression levels frequently observed in cancer...
September 30, 2016: Oncotarget
X Liu, Y Sun, L Yue, S Li, X Qi, H Zhao, Y Yang, C Zhang, H Yu
Ginsenoside Rh2 has been shown to have an anti-tumor effect on a wide range of cancers. A previous study has shown that ginsenoside Rh2 can inhibit the proliferation of the human lung adenocarcinoma A549 cell line in a dose-dependent manner by activating caspase-8/3 activity to promote apoptosis. However, the association of the JNK signaling pathways and transcription factors with ginsenoside Rh2 in the suppression of non-small cell lung cancer has not yet been reported. In this study, we found that ginsenoside Rh2 can activate the JNK/MAPKs signaling pathway and increase the phosphorylation and transcriptional activity of the transcription factors AP-1 and ATF2...
September 19, 2016: Genetics and Molecular Research: GMR
Lin-Hai Yan, Zhi-Ning Chen, Li Li, Jia Chen, Xian-Wei Mo, Yu-Zhou Qin, Wen-E Wei, Hai-Quan Qin, Yuan Lin, Jian-Si Chen
Activation of the transcription factor E2F-1 gene is a negative event in dendritic cell (DC) maturation process. Down-regulation of E2F1 causes immaturity of DC thereby stopping antigen production which in turn leads to inhibition of immune responses. E2F-1-free stimulates the NF-kB signaling pathway, leading to activation of monocytes and several other transcription factor genes. In the study, we report that down-regulation of E2F-1 in DCs promote anti-tumor immune response in gastric cancer (GC) cells through a novel mechanism...
October 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Lin-Hai Yan, Zhi-Ning Chen, Li-Li, Jia Chen, Wen-E Wei, Xian-Wei Mo, Yu-Zhou Qin, Yuan Lin, Jian-Si Chen
Resistance to oxaliplatin (OXA)-based chemotherapy regimens continues to be a major cause of gastric cancer (GC) recurrence and metastasis. We analyzed GC samples and matched non-tumorous control stomach tissues from 280 patients and found that miR-135a was overexpressed in GC samples relative to control tissues. Tumors with high miR-135a expression were more likely to have aggressive characteristics (high levels of carcino-embryonic antigen, vascular invasion, lymphatic metastasis, and poor differentiation) than those with low levels...
September 23, 2016: Oncotarget
Praween Kumar Choubey, Jagat Kumar Roy
Rab11, a small monomeric GTPase associated with recycling endosomes, is a key molecule in the regulation of vesicular trafficking and is involved in the development and differentiation of many Drosophila tissues through interaction with diverse signaling pathways. In this study, we report for the first time that Rab11 affects endoreplication through a Ras-mediated pathway. Suppression of Rab11 activity in salivary glands, an endoreplicating tissue, leads to reduction in size of salivary glands with cells having a small nucleus...
September 27, 2016: Cell and Tissue Research
Ying Yuan, Erich M Sturgis, Lijun Zhu, Meixia Lu, Yuncheng Li, Qingyi Wei, Guojun Li
Human papillomavirus (HPV) activates E2F1-driven transcription via the E7-RB1-E2F pathway. Genetic polymorphisms in the 3' untranslated region (UTR) targeted by miRNAs can affect the regulation of target genes and individual cancer risk. Thus, we hypothesized that a polymorphism at the 3'UTR miRNA binding site of E2F1 gene (rs3213180) was associated with risk of oral squamous cell carcinoma (OSCC) and tumor HPV status of oropharynx squamous cell carcinoma (OPSCC). We determined the E2F1rs3213180 polymorphism and HPV16 L1 serology of 325 OSCC patients and 335 controls, and tumor HPV16 status of 552 OPSCC...
September 28, 2016: Molecular Carcinogenesis
Dingyun You, Hongbo Zhao, Yan Wang, Yang Jiao, Minnan Lu, Shan Yan
The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator, which is overexpressed in various types of human cancers, including breast cancer. However, the molecular mechanisms regulating AIB1 function remain largely unknown. In this study, we present evidence demonstrating that AIB1 is acetylated by MOF in human breast cancer cells. Moreover, we also found that the acetylation of AIB1 enhances its function in promoting breast cancer cell proliferation. We further showed that the acetylation of AIB1 is required for its recruitment to E2F1 target genes by E2F1...
September 2016: Molecules and Cells
Ming Sun, Fengqi Nie, Yunfei Wang, Zhihong Zhang, Jiakai Hou, Dandan He, Min Xie, Wei De, Zhaoxia Wang, Jun Wang
Long noncoding RNAs (lncRNA) have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we investigated lncRNA alterations that contribute to gastric cancer (GC) through an analysis of TCGA RNA sequencing data and other publicly available microarray data. Here we report the GC-associated lncRNA HOXA11-AS as a key regulator of GC development and progression. Patients with high HOXA11-AS expression had a shorter survival and poorer prognosis. In vitro and in vivo assays of HOXA11-AS alterations revealed a complex integrated phenotype affecting cell growth, migration, invasion and apoptosis...
September 20, 2016: Cancer Research
Simone Jueliger, John Lyons, Sara Cannito, Illar Pata, Pille Pata, Marianna Shkolnaya, Oriana Lo Re, Marion Peyrou, Francesc Villarroya, Valerio Pazienza, Francesca Rappa, Francesco Cappello, Mohammad Azab, Pietro Taverna, Manlio Vinciguerra
Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine...
August 11, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Luca Malorni, Silvano Piazza, Yari Ciani, Cristina Guarducci, Martina Bonechi, Chiara Biagioni, Christopher D Hart, Roberto Verardo, Angelo Di Leo, Ilenia Migliaccio
Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib...
September 13, 2016: Oncotarget
Dong-Xu He, Guang-Yuan Zhang, Xiao-Ting Gu, Ai-Qin Mao, Chun-Xiao Lu, Jian Jin, De-Quan Liu, Xin Ma
Long non-coding RNAs (lncRNAs) are involved in cancer progression. In the present study, we analyzed the lncRNA profiles in adriamycin-resistant and -sensitive breast cancer cells and found a group of dysregulated lncRNAs in the adriamycin-resistant cells. Expression of the dysregulated lncRNAs was correlated with dysregulated mRNAs, and these were enriched in GO and KEGG pathways associated with cancer progression and chemoresistance development. Among these lncRNA-mRNA interactions, some lncRNAs may cis‑regulate neighboring protein-coding genes and be involved in chemoresistance...
August 22, 2016: International Journal of Oncology
Peck Yean Tan, Cheng Wei Chang, Kaibo Duan, Michael Poidinger, Kai Lyn Ng, Yap Seng Chong, Peter D Gluckman, Walter Stünkel
Wharton's jelly-derived Mesenchymal Stem Cells (MSCs) isolated from newborns with intrauterine fetal growth restriction were previously shown to exert anabolic features including insulin hypersensitivity. Here, we extend these observations and demonstrate that MSCs from small for gestational age (SGA) individuals have decreased mitochondrial oxygen consumption rates. Comparing normally grown and SGA MSCs using next generation sequencing studies, we measured global transcriptomic and epigenetic profiles and identified E2F1 as an over-expressed transcription factor regulating oxidative metabolism in the SGA group...
2016: PloS One
Ling-Yu Wang, Chiu-Lien Hung, Yun-Ru Chen, Joy C Yang, Junjian Wang, Mel Campbell, Yoshihiro Izumiya, Hong-Wu Chen, Wen-Ching Wang, David K Ann, Hsing-Jien Kung
The histone lysine demethylase KDM4A/JMJD2A has been implicated in prostate carcinogenesis through its role in transcriptional regulation. Here, we describe KDM4A as a E2F1 coactivator and demonstrate a functional role for the E2F1-KDM4A complex in the control of tumor metabolism. KDM4A associates with E2F1 on target gene promoters and enhances E2F1 chromatin binding and transcriptional activity, thereby modulating the transcriptional profile essential for cancer cell proliferation and survival. The pyruvate dehydrogenase kinases (PDKs) PDK1 and PDK3 are direct targets of KDM4A and E2F1 and modulate the switch between glycolytic metabolism and mitochondrial oxidation...
September 13, 2016: Cell Reports
Xin Wang, Ji Sun, Meiling Cui, Fangyu Zhao, Chao Ge, Taoyang Chen, Ming Yao, Jinjun Li
Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known about the mechanism of FOXP1 in the proliferation of HCC cells. This study aimed to further explore the function of FOXP1 on the proliferation of HCC cells as well as the relevant mechanism involved...
2016: International Journal of Molecular Sciences
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