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https://www.readbyqxmd.com/read/28176176/amplification-of-sox4-promotes-pi3k-akt-signaling-in-human-breast-cancer
#1
Gaurav A Mehta, Joel S Parker, Grace O Silva, Katherine A Hoadley, Charles M Perou, Michael L Gatza
PURPOSE: The PI3K/Akt signaling axis contributes to the dysregulation of many dominant features in breast cancer including cell proliferation, survival, metabolism, motility, and genomic instability. While multiple studies have demonstrated that basal-like or triple-negative breast tumors have uniformly high PI3K/Akt activity, genomic alterations that mediate dysregulation of this pathway in this subset of highly aggressive breast tumors remain to be determined. METHODS: In this study, we present an integrated genomic analysis based on the use of a PI3K gene expression signature as a framework to analyze orthogonal genomic data from human breast tumors, including RNA expression, DNA copy number alterations, and protein expression...
February 7, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28157484/small-molecules-modulate-chromatin-accessibility-to-promote-neurog2-mediated-fibroblast-to-neuron-reprogramming
#2
Derek K Smith, Jianjing Yang, Meng-Lu Liu, Chun-Li Zhang
Pro-neural transcription factors and small molecules can induce the reprogramming of fibroblasts into functional neurons; however, the immediate-early molecular events that catalyze this conversion have not been well defined. We previously demonstrated that neurogenin 2 (NEUROG2), forskolin (F), and dorsomorphin (D) can reprogram fibroblasts into functional neurons with high efficiency. Here, we used this model to define the genetic and epigenetic events that initiate an acquisition of neuronal identity. We demonstrate that NEUROG2 is a pioneer factor, FD enhances chromatin accessibility and H3K27 acetylation, and synergistic transcription activated by these factors is essential to successful reprogramming...
November 8, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/28133610/histological-and-pathological-assessment-of-mir-204-and-sox4-levels-in-gastric-cancer-patients
#3
Xiao Yuan, Shuanhu Wang, Mulin Liu, Zhen Lu, Yanqing Zhan, Wenbin Wang, A-Man Xu
Gastric cancer is one of the most common cancers and the efficient therapeutic methods are limited. Further study of the exact molecular mechanism of gastric cancer to develop novel targeted therapies is necessary and urgent. We herein systematically examined that miR-204 suppressed both proliferation and metastasis of gastric cancer AGS cells. miR-204 directly targeted SOX4. In clinical tissue research, we determined that miR-204 was expressed much lower and SOX4 expressed much higher in gastric cancer tissues compared with normal gastric tissues...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28118982/sox4-regulates-gonad-morphogenesis-and-promotes-male-germ-cell-differentiation-in-mice
#4
Liang Zhao, Michel Arsenault, Ee Ting Ng, Enya Longmuss, Tevin Chui-Ying Chau, Sunny Hartwig, Peter Koopman
The group C SOX transcription factors SOX4, -11 and -12 play important and mutually overlapping roles in development of a number of organs. Here, we examined the role of SoxC genes during gonadal development in mice. All three genes were expressed in developing gonads of both sexes, predominantly in somatic cells, with Sox4 being most strongly expressed. Sox4 deficiency resulted in elongation of both ovaries and testes, and an increased number of testis cords. While female germ cells entered meiosis normally, male germ cells showed reduced levels of differentiation markers Nanos2 and Dnmt3l and increased levels of pluripotency genes Cripto and Nanog, suggesting that SOX4 may normally act to restrict the pluripotency period of male germ cells and ensure their proper differentiation...
January 21, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28118321/propofol-suppresses-esophageal-squamous-cell-carcinoma-cell-migration-and-invasion-by-down-regulation-of-sex-determining-region-y-box-4-sox4
#5
Chun-Li Zhou, Jing-Jing Li, Peng Ji
BACKGROUND This study was done to verify whether propofol could inhibit esophageal squamous cell carcinoma (ESCC) cell line EC9706 cell migration and invasion by targeting SOX4. MATERIAL AND METHODS Different concentrations of propofol were co-incubated with EC9706 cells. The pcDNA-SOX4 or SOX4 siRNA plasmid was transfected into cells before the treatment with propofol 5 µg/L. The migratory and invasion ability of EC9706 cells were tested by wound-healing assay and Transwell chambers. Western blotting was used to investigate the expressions of MMP-2, MMP-9, TIMP-1, TIMP-2, and SOX4...
January 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28105216/identification-of-potential-therapeutic-targets-for-colorectal-cancer-by-bioinformatics-analysis
#6
Ming Yan, Maomin Song, Rixing Bai, Shi Cheng, Wenmao Yan
The aim of the present study was to identify potential therapeutic targets for colorectal cancer (CRC). The gene expression profile GSE32323, containing 34 samples, including 17 specimens of CRC tissues and 17 of paired normal tissues from CRC patients, was downloaded from the Gene Expression Omnibus database. Following data preprocessing using the Affy and preprocessCore packages, the differentially-expressed genes (DEGs) between the two types of samples were identified with the Linear Models for Microarray Analysis package...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#7
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28038442/mutations-acquired-by-hepatocellular-carcinoma-recurrence-give-rise-to-an-aggressive-phenotype
#8
Ji-Hye Choi, Min Jae Kim, Yong Keun Park, Jong-Yeop Im, So Mee Kwon, Hyung Chul Kim, Hyun Goo Woo, Hee-Jung Wang
Recurrence of hepatocellular carcinoma (HCC) even after curative resection causes dismal outcomes of patients. Here, to delineate the driver events of genomic and transcription alteration during HCC recurrence, we performed RNA-Seq profiling of the paired primary and recurrent tumors from two patients with intrahepatic HCC. By comparing the mutational and transcriptomic profiles, we identified somatic mutations acquired by HCC recurrence including novel mutants of GOLGB1 (E2721V) and SF3B3 (H804Y). By performing experimental evaluation using siRNA-mediated knockdown and overexpression constructs, we demonstrated that the mutants of GOLGB1 and SF3B3 can promote cell proliferation, colony formation, migration, and invasion of liver cancer cells...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27982693/long-noncoding-rna-dancr-is-a-positive-regulator-of-proliferation-and-chondrogenic-differentiation-in-human-synovium-derived-stem-cells
#9
Lei Zhang, Chao Yang, Shuo Chen, Guihua Wang, Ben Shi, Xin Tao, Liwu Zhou, Jianning Zhao
Cartilage tissues have limited capacity for repair after damage and then cause osteoarthritis, so finding alternative treatment is ongoing. Mesenchymal stem cells (MSCs) have become a promising therapy for cartilage damage and diseases due to the advantages of easy separation, high proliferative potentiality, and genetic stability. Synovium-derived MSCs (SMSCs) have been recognized as an ideal source for cartilage repair. In our previous study, we found that Sox4 promoted proliferation and chondrogenesis of SMSCs through upregulation of long noncoding RNA (lncRNA) DANCR...
February 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/27907195/novel-aryl-hydrocarbon-receptor-agonist-suppresses-migration-and-invasion-of-breast-cancer-cells
#10
Hamza Hanieh, Omar Mohafez, Villianur Ibrahim Hairul-Islam, Abdullah Alzahrani, Mohammad Bani Ismail, Krishnaraj Thirugnanasambantham
BACKGROUND: Despite the remarkable progress to fight against breast cancer, metastasis remains the dominant cause of treatment failure and recurrence. Therefore, control of invasiveness potential of breast cancer cells is crucial. Accumulating evidences suggest Aryl hydrocarbon receptor (Ahr), a helix-loop-helix transcription factor, as a promising target to control migration and invasion in breast cancer cells. Thus, an Ahr-based exploration was performed to identify a new Ahr agonist with inhibitory potentials on cancer cell motility...
2016: PloS One
https://www.readbyqxmd.com/read/27873024/p4%C3%A2-medicine-and-osteoporosis-a%C3%A2-systematic-review
#11
REVIEW
Klemen Kodrič, Klemen Čamernik, Darko Černe, Radko Komadina, Janja Marc
BACKGROUND: Osteoporosis is the most frequent bone metabolic disease. In order to improve early detection, prediction, prevention, diagnosis, and treatment of the disease, a new model of P4 medicine (personalized, predictive, preventive, and participatory medicine) could be applied. The aim of this work was to systematically review the publications of four different types of "omics" studies related to osteoporosis, in order to discover novel predictive, preventive, diagnostic, and therapeutic targets for better management of the geriatric population...
December 2016: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/27831649/mir-129-5p-is-downregulated-in-breast-cancer-cells-partly-due-to-promoter-h3k27m3-modification-and-regulates-epithelial-mesenchymal-transition-and-multi-drug-resistance
#12
Q-X Luan, B-G Zhang, X-J Li, M-Y Guo
OBJECTIVE: In this study, we firstly studied whether H3K27me3 modification is a mechanism of miR-129-5p downregulation in breast cancer and further investigated the functional role of miR-129-5p in epithelial-to-mesenchymal transition (EMT) and in multi-drug resistance (MDR) of the cancer cells. MATERIALS AND METHODS: Immunoprecipitation (IP) and Chromatin Immunoprecipitation (ChIP) assay were performed to detect the association among SOX4, EZH2 and H3K27me3 and their enrichment in the promoter region of miR-129-2...
October 2016: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/27827314/lncrnas-as-novel-indicators-of-patients-prognosis-in-stage-i-epithelial-ovarian-cancer-a-retrospective-and-multicentric-study
#13
Paolo Martini, Lara Paracchini, Giulia Caratti, Maurizia Mello-Grand, Robert Fruscio, Luca Beltrame, Enrica Calura, Gabriele Sales, Antonella Ravaggi, Eliana Bignotti, Franco E Odicino, Enrico Sartori, Patrizia Perego, Dionyssios Katsaros, Ilaria Craparotta, Giovanna Chiorino, Stefano Cagnin, Laura Mannarino, Lorenzo Ceppi, Costantino Mangioni, Chiara Ghimenti, Maurizio D'Incalci, Sergio Marchini, Chiara Romualdi
PURPOSE: Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC hsa-miR-200c-3p can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNAs) to enable potential definition of a non coding transcriptional signature with prognostic relevance for stage I EOC...
November 8, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27812929/mir-212-132-is-epigenetically-downregulated-by-sox4-ezh2-h3k27me3-feedback-loop-in-ovarian-cancer-cells
#14
Lin Lin, Zhiwen Wang, Haihong Jin, Hongzhen Shi, Zhihong Lu, Zhenqin Qi
Both miR-212 and miR-132 are usually downregulated in ovarian cancer and act as tumor suppressors. However, the mechanism of their downregulation in ovarian cancer is not clear. In this study, we investigated the regulative effects of miR-212 and miR-132 on SOX4 expression in ovarian cancer cells and also studied whether there is a feedback regulation between miR-212/miR-132 and SOX4 via an epigenetic mechanism. The results showed that both EZH2 and SOX4 overexpressions significantly repressed miR-212 and miR-132 expressions in SKOV3 and OV2008 cells...
November 3, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/27743342/expression-of-soxc-transcription-factors-during-zebrafish-retinal-and-optic-nerve-regeneration
#15
Zhaoxia Mu, Shuqiang Zhang, Chunjiao He, Haitao Hou, Dong Liu, Nan Hu, Hui Xu
The SoxC transcription factors (Sox4, Sox11, and Sox12) play important roles in the development of the vertebrate eye and retina. However, their expression and function during retinal and optic nerve regeneration remain elusive. In this study, we investigated the expression and possible functions of the SoxC genes after retinal and optic nerve injury in adult zebrafish. We found that among the five SoxC members, Sox11b was strongly induced in BrdU-positive cells in the inner nuclear layer (INL) after retinal injury, and morpholino-mediated Sox11b-knockdown significantly reduced the number of proliferating cells in the INL at 4 days post-injury...
October 14, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/27667646/lncrna-uca1-enhances-cell-proliferation-through-functioning-as-a-cerna-of-sox4-in-esophageal-cancer
#16
Changjie Jiao, Zhiming Song, Jianming Chen, Jing Zhong, Weibin Cai, Suke Tian, Songlin Chen, Yunfeng Yi, Yun Xiao
Esophageal cancer (EC) is one of the most common gastrointestinal cancers, which leads to the sixth ranking of cancer-related death. Long non-coding RNAs (lncRNAs) play pivotal roles in many biological processes. lncRNA human urothelial carcinoma associated 1 (UCA1) is significantly upregulated and functions as an important oncogene in many types of human cancers. However, the role of UCA1 in EC and its underlying mechanism remains unclear. In the present study, we demonstrated that UCA1 was significantly upregulated in EC tissues and associated with poor prognosis...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27553854/lncsox4-promotes-the-self-renewal-of-liver-tumour-initiating-cells-through-stat3-mediated-sox4-expression
#17
Zhen-Zhen Chen, Lan Huang, Ya-Hong Wu, Wen-Jie Zhai, Ping-Ping Zhu, Yan-Feng Gao
Liver cancer has a tendency to develop asymptomatically in patients, so most patients are diagnosed at a later stage. Accumulating evidence implicates that liver tumour-initiating cells (TICs) as being responsible for liver cancer initiation and recurrence. However, the molecular mechanism of liver TIC self-renewal is poorly understood. Here we discover that a long noncoding RNA (lncRNA) termed LncSox4 is highly expressed in hepatocellular carcinoma (HCC) tissues and in liver TICs. We find that LncSox4 is required for liver TIC self-renewal and tumour initiation...
2016: Nature Communications
https://www.readbyqxmd.com/read/27527117/microrna-132-212-upregulation-inhibits-tgf-%C3%AE-mediated-epithelial-mesenchymal-transition-of-prostate-cancer-cells-by-targeting-sox4
#18
Weiwei Fu, Tao Tao, Mei Qi, Lin Wang, Jing Hu, Xinjun Li, Naidong Xing, Ran Du, Bo Han
BACKGROUND: MicroRNAs (miRNAs) are noncoding RNAs that are important for embryonic stem cell development and epithelial to mesenchymal transition (EMT). Accumulating evidence indicates that miRNAs play critical roles in prostate cancer (PCa) metastasis and have potential use as therapeutic targets. Although dysregulated miR-132/212 have been suggested to be directly involved in the proliferation and invasion of multiple malignancies, the exact role of miR-132/212 in PCa has not yet been fully understood...
December 2016: Prostate
https://www.readbyqxmd.com/read/27508100/erratum-microrna-338-3p-suppresses-metastasis-of-lung-cancer-cells-by-targeting-the-emt-regulator-sox4
#19
Yang Li, Peirui Chen, Lingling Zu, Bin Liu, Min Wang, Qinghua Zhou
[This corrects the article on p. 127 in vol. 6, PMID: 27186391.].
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27484700/mapping-epigenetic-changes-to-the-host-cell-genome-induced-by-burkholderia-pseudomallei-reveals-pathogen-specific-and-pathogen-generic-signatures-of-infection
#20
Deniz Cizmeci, Emma L Dempster, Olivia L Champion, Sariqa Wagley, Ozgur E Akman, Joann L Prior, Orkun S Soyer, Jonathan Mill, Richard W Titball
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling...
2016: Scientific Reports
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