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Takahiro Kishikawa, Motoyuki Otsuka, Takeshi Yoshikawa, Motoko Ohno, Hideaki Ijichi, Kazuhiko Koike
Highly repetitive tandem arrays at the centromeric and pericentromeric regions in chromosomes, previously considered silent, are actively transcribed, particularly in cancer. This aberrant expression occurs even in K-ras-mutated pancreatic intraepithelial neoplasia (PanIN) tissues, which are precancerous lesions. To examine the biological roles of the satellite RNAs in carcinogenesis, we construct mouse PanIN-derived cells expressing major satellite (MajSAT) RNA and show increased malignant properties. We find an increase in frequency of chromosomal instability and point mutations in both genomic and mitochondrial DNA...
2016: Nature Communications
Nahid Safari-Alighiarloo, Mohammad Taghizadeh, Seyyed Mohammad Tabatabaei, Soodeh Shahsavari, Saeed Namaki, Soheila Khodakarim, Mostafa Rezaei-Tavirani
BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic beta cells are destroyed by infiltrating immune cells. Bilateral cooperation of pancreatic beta cells and immune cells has been proposed in progression of T1D, but there is no systems study to investigate it. Here, we aimed to explicate etiological molecular basis and identify key genes associated to T1D risk by network biology approach in two circumstances. METHODS: We integrated interactome (protein-protein interaction (PPI)) and transcriptomes data data of transcriptomes to construct networks of differentially expressed genes in peripheral blood mononuclear cells (PBMCs) and pancreatic beta cells...
September 14, 2016: Journal of Diabetes
Siting Li, Minghai Chen, Qian Xiong, Jia Zhang, Zongqiang Cui, Feng Ge
Translationally controlled tumor protein (TCTP) is a highly conserved housekeeping protein present in eukaryotic organisms. It is involved in regulating many fundamental processes and plays a critical role in tumor reversion and tumorigenesis. Increasing evidence suggests that TCTP plays a role in the regulation of cell fate determination and is a promising therapeutic target for cancer. To decipher the exact mechanisms by which TCTP functions and how all these functions are integrated, we analyzed the interactome of TCTP in HeLa cells by coimmunoprecipitation (IP) and mass spectrometry (MS)...
October 7, 2016: Journal of Proteome Research
Matthew J Shurtleff, Morayma M Temoche-Diaz, Kate V Karfilis, Sayaka Ri, Randy Schekman
Exosomes are small vesicles that are secreted from metazoan cells and may convey selected membrane proteins and small RNAs to target cells for the control of cell migration, development and metastasis. To study the mechanisms of RNA packaging into exosomes, we devised a purification scheme based on the membrane marker CD63 to isolate a single exosome species secreted from HEK293T cells. Using immunoisolated CD63-containing exosomes we identified a set of miRNAs that are highly enriched with respect to their cellular levels...
August 25, 2016: ELife
S-L Liu, Y-F Sui, M-Z Lin
OBJECTIVE: In this study, we firstly verified how miR-375 is downregulated in breast cancer cells with multi-drug resistance (MDR) and further investigated the regulative effect of miR-375 on Ybx1 expression. MATERIALS AND METHODS: MiR-375 expression and promoter methylation status were studied by retrieving data in NCBI GEO Datasets, qRT-PCR and Methylation-Specific PCR (MSP) assay. Drug sensitivity of the cancer cells was assessed using MTT assay. The binding between miR-375 and YBX1 gene was predicted using Targetscan 7...
July 2016: European Review for Medical and Pharmacological Sciences
Yihan Ma, Peiqi Xu, Yanjun Mi, Wenyi Wang, Xiaoyan Pan, Xiaoting Wu, Qi He, Hongming Liu, Weiwei Tang, Hanxiang An
Based on recognition of driver mutations, treatment paradigm for non-small-cell lung cancer (NSCLC) patients has been shifted. However, recently exon 19 deletion mutation (del19) of epidermal growth factor receptor (EGFR) clearly shows better clinical benefit over single-point substitution mutation L858R in exon 21 (L858R). The aim of this study was to investigate the difference by analyzing the expression of plasma microRNAs (miRNAs) of NSCLC patients with EGFR mutation del19 or L858R. MiRNA microarray of plasma from patients' blood identified 79 mapped, network-eligible miRNAs (fold > 5), of which 76 were up regulated and 3 were down regulated...
July 24, 2016: Oncotarget
Shilei Zhao, Yan Wang, Tao Guo, Wendan Yu, Jinxiu Li, Zhipeng Tang, Zhenlong Yu, Lei Zhao, Yixiang Zhang, Ziyi Wang, Peng Wang, Yechi Li, Fengzhou Li, Zhe Sun, Yang Xuan, Ranran Tang, Wu-Guo Deng, Wei Guo, Chundong Gu
Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression...
June 15, 2016: Oncotarget
Shilei Zhao, Wei Guo, Jinxiu Li, Wendan Yu, Tao Guo, Wuguo Deng, Chundong Gu
BACKGROUND: Prognosis of small (≤2 cm) invasive lung adenocarcinoma remains poor, and identification of high-risk individuals from the patients after complete surgical resection of lung adenocarcinoma has become an urgent problem. YBX1 has been reported to be able to predict prognosis in many cancers (except lung adenocarcinoma) that are independent of TNM (tumor, nodes, metastases) staging, especially small invasive lung adenocarcinoma. Therefore, we examined the significance of YBX1 expression on prognosis and recurrence in patients with small invasive lung adenocarcinoma...
2016: OncoTargets and Therapy
B Pfaffenseller, P V da Silva Magalhães, M A De Bastiani, M A A Castro, A L Gallitano, F Kapczinski, F Klamt
Bipolar disorder (BD) is a severe mental illness with a strong genetic component. Despite its high degree of heritability, current genetic studies have failed to reveal individual loci of large effect size. In lieu of focusing on individual genes, we investigated regulatory units (regulons) in BD to identify candidate transcription factors (TFs) that regulate large groups of differentially expressed genes. Network-based approaches should elucidate the molecular pathways governing the pathophysiology of BD and reveal targets for potential therapeutic intervention...
2016: Translational Psychiatry
Annette Lasham, Sunali Y Mehta, Sandra J Fitzgerald, Adele G Woolley, James I Hearn, Daniel G Hurley, Igor Ruza, Michael Algie, Andrew N Shelling, Antony W Braithwaite, Cristin G Print
Chemotherapy with taxanes such as paclitaxel (PTX) is a key component of triple negative breast cancer (TNBC) treatment. PTX is used in combination with other drugs in both the adjuvant setting and in advanced breast cancer. Because a proportion of patients respond poorly to PTX or relapse after its use, a greater understanding of the mechanisms conferring resistance to PTX is required. One protein shown to be involved in drug resistance is Y-box binding protein 1 (YB-1). High levels of YB-1 have previously been associated with resistance to PTX in TNBCs...
September 1, 2016: International Journal of Cancer. Journal International du Cancer
Jing Liu, Xiangdong Sun, Hongcheng Zhu, Qin Qin, Xi Yang, Xinchen Sun
Esophageal carcinoma is one of the most lethal cancer types in the world, especially in some part of China. Esophageal squamous cell carcinoma is a major subtype, which has been shown to be associated with unhealthy diet habit, smoking, environmental carcinogens etc. The esophageal squamous cell carcinoma (ESCC) often progress slowly, however, it is often diagnosed at an advanced stage. Thus it is imperative to elucidate the molecular mechanisms involved in the initiation and progression of ESCC. Long noncoding RNAs (lncRNA) has emerged as a novel functional player transcribed from the genome...
March 31, 2016: Journal of Biochemistry
Shashi K Gopal, David W Greening, Eric G Hanssen, Hong-Jian Zhu, Richard J Simpson, Rommel A Mathias
The metastatic cascade describes the escape of primary tumour cells to distant secondary sites. Cells at the leading tumour edge are thought to undergo epithelial-mesenchymal transition (EMT), to enhance their motility and invasion for spreading. Whether EMT cells directly promote tumour angiogenesis, and the role of exosomes (30-150 nm extracellular vesicles) remains largely unknown. We examined the functional effects of exosomes from MDCK cells, MDCK cells stably expressing YBX1 (MDCKYBX1, intermediate EMT), and Ras-transformed MDCK cells (21D1 cells, complete EMT)...
April 12, 2016: Oncotarget
F Roßner, C Gieseler, M Morkel, H-D Royer, M Rivera, H Bläker, M Dietel, R Schäfer, C Sers
The transcription factor YBX1 can act as a mediator of signals transmitted via the EGFR-RAS-MAPK axis. YBX1 expression has been associated with tumor progression and prognosis in multiple types of cancer. Immunohistochemical studies have revealed dependency between YBX1 expression and individual EGFR family members. We analyzed YBX1 and EGFR family proteins in a colorectal cancer (CRC) cohort and provide functional analyses of YBX1 in the context of EGFR-RAS-MAPK signaling. Immunohistochemistry for YBX1 and EGFR family receptors with two antibodies for YBX1 and EGFR were performed and related to clinicopathological data...
2016: Oncogenesis
Lakshmi Prabhu, Rasika Mundade, Benlian Wang, Han Wei, Antja-Voy Hartley, Matthew Martin, Kyle McElyea, Constance J Temm, George Sandusky, Yunlong Liu, Tao Lu
Y-box binding protein 1 [YBX1] is a multifunctional protein known to facilitate many of the hallmarks of cancer. Elevated levels of YBX1 protein are highly correlated with cancer progression, making it an excellent marker in cancer. The connection between YBX1 and the important nuclear factor κB [NF-κB] has never been reported. Here, we show that overexpression of wild type YBX1 [WT-YBX1] activates NF-κB, suggesting that YBX1 is a potential NF-κB activator. Furthermore, using mass spectrometry analysis we identified novel phosphorylation of serine 165 [S165] on YBX1...
October 6, 2015: Oncotarget
Chuanliang Guo, Yan Xue, Guanheng Yang, Shang Yin, Wansheng Shi, Yan Cheng, Xiaoshuang Yan, Shuyue Fan, Huijun Zhang, Fanyi Zeng
Nanog is a well-known transcription factor that plays a fundamental role in stem cell self-renewal and the maintenance of their pluripotent cell identity. There remains a large data gap with respect to the spectrum of the key pluripotency transcription factors' interaction partners. Limited information is available concerning Nanog-associated RNA-binding proteins (RBPs), and the intrinsic protein-RNA interactions characteristic of the regulatory activities of Nanog. Herein, we used an improved affinity protocol to purify Nanog-interacting RBPs from mouse embryonic stem cells (ESCs), and 49 RBPs of Nanog were identified...
August 2016: Cell Biology International
Marie van Dijk, Allerdien Visser, Kwadwo M L Buabeng, Ankie Poutsma, Roel C van der Schors, Cees B M Oudejans
LINC-HELLP, showing chromosomal linkage with the pregnancy-specific HELLP syndrome in Dutch families, reduces differentiation from a proliferative to an invasive phenotype of first-trimester extravillous trophoblasts. Here we show that mutations in LINC-HELLP identified in HELLP families negatively affect this trophoblast differentiation either by inducing proliferation rate or by causing cell cycle exit as shown by a decrease in both proliferation and invasion. As LincRNAs predominantly function through interactions with proteins, we identified the directly interacting proteins using chromatin isolation by RNA purification followed by protein mass spectrometry...
October 1, 2015: Human Molecular Genetics
Lijie He, Mingwen Che, Jinping Hu, Sutong Li, Zhen Jia, Weijuan Lou, Cuixiang Li, Jun Yang, Shiren Sun, Hanmin Wang, Xiangmei Chen
Twist is overexpressed in high glucose (HG) damage of human peritoneal mesothelial cells (HPMCs) in vitro. Herein, we further identified its precise function related to fibrosis of peritoneal membranes (PMs). The overexpression and activation of Twist and YB-1 (official name, YBX1) and a transformed fibroblastic phenotype of HPMCs were found to be positively related to epithelial-mesenchymal transition progress and PM fibrosis ex vivo in 93 patients who underwent continuous ambulatory peritoneal dialysis (PD), and also in HG-induced immortal HPMCs and an animal model of PD...
August 2015: American Journal of Pathology
Shashi K Gopal, David W Greening, Rommel A Mathias, Hong Ji, Alin Rai, Maoshan Chen, Hong-Jian Zhu, Richard J Simpson
Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nuclease-sensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCKYBX1 cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth...
May 30, 2015: Oncotarget
Yongchao Liu, Jing Zhao, Wenhong Zhang, Jun Gan, Chengen Hu, Guangjian Huang, Ying Zhang
Long non-coding RNAs (lncRNAs), which have evolved as important gene expression modulators, are involved in human malignancies. The down-regulation of lncRNA growth arrest specific transcript 5 (GAS5) has been reported in several cancers, however, the underlying mechanism of lncRNA GAS5 in stomach cancer is poorly understood. In this study, we found that lncRNA GAS5 had lower expression in stomach cancer tissues than the normal counterparts. lncRNA GAS5 was shown to interact with Y-box binding protein 1 (YBX1), and lncRNA GAS5 knockdown was shown to accelerate YBX1 protein turnover without affecting YBX1 transcription...
2015: Scientific Reports
Hani Goodarzi, Xuhang Liu, Hoang C B Nguyen, Steven Zhang, Lisa Fish, Sohail F Tavazoie
Upon exposure to stress, tRNAs are enzymatically cleaved, yielding distinct classes of tRNA-derived fragments (tRFs), yielding distinct classes of tRFs. We identify a novel class of tRFs derived from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) that, upon induction, suppress the stability of multiple oncogenic transcripts in breast cancer cells by displacing their 3' untranslated regions (UTRs) from the RNA-binding protein YBX1. This mode of post-transcriptional silencing is sequence specific, as these fragments all share a common motif that matches the YBX1 recognition sequence...
May 7, 2015: Cell
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