scholarly journals Down regulation of RNA binding motif, single-stranded interacting protein 3, along with up regulation of nuclear HIF1A correlates with poor prognosis in patients with gastric cancer

Oncotarget ◽  
2016 ◽  
Vol 8 (1) ◽  
pp. 1262-1277 ◽  
Author(s):  
Youliang Wu ◽  
Dapeng Yun ◽  
Yingjie Zhao ◽  
Yuqi Wang ◽  
Ruochuan Sun ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Rna Binding ◽  
Binding Motif ◽  
Down Regulation ◽  
Interacting Protein

scholarly journals A novel member of the SAF (scaffold attachment factor)-box protein family inhibits gene expression and induces apoptosis

2007 ◽  
Vol 407 (3) ◽  
pp. 355-362 ◽  
Author(s):  
Ching Wan Chan ◽  
Youn-Bok Lee ◽  
James Uney ◽  
Andrea Flynn ◽  
Jonathan H. Tobias ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rna Binding ◽  
Chromatin Condensation ◽  
Inhibitory Effect ◽  
Binding Motif ◽  
Inhibitory Effects ◽  
Cytochrome C Release ◽  
Interacting Protein ◽  
Induced Apoptosis ◽  
Attachment Factor

The SLTM [SAF (scaffold attachment factor)-like transcription modulator] protein contains a SAF-box DNA-binding motif and an RNA-binding domain, and shares an overall identity of 34% with SAFB1 {scaffold attachment factor-B1; also known as SAF-B (scaffold attachment factor B), HET [heat-shock protein 27 ERE (oestrogen response element) and TATA-box-binding protein] or HAP (heterogeneous nuclear ribonucleoprotein A1-interacting protein)}. Here, we show that SLTM is localized to the cell nucleus, but excluded from nucleoli, and to a large extent it co-localizes with SAFB1. In the nucleus, SLTM has a punctate distribution and it does not co-localize with SR (serine/arginine) proteins. Overexpression of SAFB1 has been shown to exert a number of inhibitory effects, including suppression of oestrogen signalling. Although SLTM also suppressed the ability of oestrogen to activate a reporter gene in MCF-7 breast-cancer cells, inhibition of a constitutively active β-galactosidase gene suggested that this was primarily the consequence of a generalized inhibitory effect on transcription. Measurement of RNA synthesis, which showed a particularly marked inhibition of [3H]uridine incorporation into mRNA, supported this conclusion. In addition, analysis of cell-cycle parameters, chromatin condensation and cytochrome c release showed that SLTM induced apoptosis in a range of cultured cell lines. Thus the inhibitory effects of SLTM on gene expression appear to result from generalized down-regulation of mRNA synthesis and initiation of apoptosis consequent upon overexpressing the protein. While indicating a crucial role for SLTM in cellular function, these results also emphasize the need for caution when interpreting phenotypic changes associated with manipulation of protein expression levels.

Loss of RNA-binding motif protein 3 expression is associated with right-sided localization and poor prognosis in colorectal cancer

2015 ◽  
Vol 68 (2) ◽  
pp. 191-198 ◽  
Author(s):  
Nathaniel Melling ◽  
Ronald Simon ◽  
Martina Mirlacher ◽  
Jakob R Izbicki ◽  
Philip Stahl ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Rna Binding ◽  
Binding Motif

scholarly journals The Aberrant Expression of MicroRNA-125a-5p/IGF2BP3 Axis in Advanced Gastric Cancer and Its Clinical Relevance

2020 ◽  
Vol 19 ◽  
pp. 153303382091733
Author(s):  
Jing Zhang ◽  
Fanghui Ding ◽  
Dan Jiao ◽  
Qiaozhi Li ◽  
Hong Ma
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Advanced Gastric Cancer ◽  
Messenger Rna ◽  
Poor Prognosis ◽  
Rna Binding ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Advanced Stage ◽  
Insulin Like Growth Factor

RNA-binding proteins have been associated with cancer development. The overexpression of a well-known RNA-binding protein, insulin-like growth factor 2 messenger RNA–binding protein 3, has been identified as an indicator of poor prognosis in patients with various types of cancer. Although gastric cancer is a relatively frequent and potentially fatal malignancy, the mechanism by which insulin-like growth factor 2 messenger RNA–binding protein 3 regulates the development of this cancer remains unclear. This study aimed to investigate the role and regulatory mechanism of insulin-like growth factor 2 messenger RNA–binding protein 3 in gastric cancer. An analysis of IGF2BP3 expression patterns reported in 4 public gastric cancer–related microarray data sets from the Gene Expression Omnibus and The Cancer Genome Atlas-Stomach Adenocarcinoma revealed strong expression of this gene in gastric cancer tissues. Insulin-like growth factor 2 messenger RNA–binding protein 3 expression in gastric cancer was further confirmed via quantitative reverse transcription polymerase chain reaction and immunohistochemistry, respectively, in an in-house gastric cancer cohort (n = 30), and the association of insulin-like growth factor 2 messenger RNA–binding protein 3 expression with clinical parameters and prognosis was analyzed. Notably, stronger IGF2BP3 expression significantly correlated with poor prognosis, and significant changes in insulin-like growth factor 2 messenger RNA–binding protein 3 expression were only confirmed in patients with advanced-stage gastric cancer in an independent cohort. The effects of insulin-like growth factor 2 messenger RNA–binding protein 3 on cell proliferation were confirmed through in vitro experiments involving the HGC-27 gastric cancer cell line. MicroR-125a-5p, a candidate microRNA that target on insulin-like growth factor 2 messenger RNA–binding protein 3, decreased in advanced-stage gastric cancer. Upregulation of microR-125a-5p inhibited insulin-like growth factor 2 messenger RNA–binding protein 3, and dual-luciferase report assay indicated that microR-125a-5p inhibited the translation of IGF2BP3 by directly targeting the 3′ untranslated region. These results indicate that the microR-125a-5p/insulin-like growth factor 2 messenger RNA–binding protein 3 axis contributes to the oncogenesis of advanced gastric cancer.

scholarly journals Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769454 ◽  
Author(s):  
Takahiko Kobayashi ◽  
Junich Ishida ◽  
Yuichi Shimizu ◽  
Hiroshi Kawakami ◽  
Goki Suda ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Protein Expression ◽  
Cancer Cells ◽  
Rna Binding ◽  
Suppressor Gene ◽  
Binding Motif ◽  
Gastric Cancer Cells ◽  
Rna Binding Motif 5

RNA-binding motif 5 is a putative tumor suppressor gene that modulates cell cycle arrest and apoptosis. We recently demonstrated that RNA-binding motif 5 inhibits cell growth through the p53 pathway. This study evaluated the clinical significance of RNA-binding motif 5 expression in gastric cancer and the effects of altered RNA-binding motif 5 expression on cancer biology in gastric cancer cells. RNA-binding motif 5 protein expression was evaluated by immunohistochemistry using the surgical specimens of 106 patients with gastric cancer. We analyzed the relationships of RNA-binding motif 5 expression with clinicopathological parameters and patient prognosis. We further explored the effects of RNA-binding motif 5 downregulation with short hairpin RNA on cell growth and p53 signaling in MKN45 gastric cancer cells. Immunohistochemistry revealed that RNA-binding motif 5 expression was decreased in 29 of 106 (27.4%) gastric cancer specimens. Decreased RNA-binding motif 5 expression was correlated with histological differentiation, depth of tumor infiltration, nodal metastasis, tumor–node–metastasis stage, and prognosis. RNA-binding motif 5 silencing enhanced gastric cancer cell proliferation and decreased p53 transcriptional activity in reporter gene assays. Conversely, restoration of RNA-binding motif 5 expression suppressed cell growth and recovered p53 transactivation in RNA-binding motif 5–silenced cells. Furthermore, RNA-binding motif 5 silencing reduced the messenger RNA and protein expression of the p53 target gene p21. Our results suggest that RNA-binding motif 5 downregulation is involved in gastric cancer progression and that RNA-binding motif 5 behaves as a tumor suppressor gene in gastric cancer.

scholarly journals Down-regulation of miR-326 is associated with poor prognosis and promotes growth and metastasis by targeting FSCN1 in gastric cancer

2015 ◽  
Vol 33 (4) ◽  
pp. 267-274 ◽  
Author(s):  
Yanliang Li ◽  
Yongsheng Gao ◽  
Yue Xu ◽  
Heng Ma ◽  
Mingshan Yang
Keyword(s):  
Gastric Cancer ◽  
Poor Prognosis ◽  
Down Regulation

Interactome Analysis of the Differentially Expressed Proteins in Uterine Leiomyoma

2019 ◽  
Vol 19 (10) ◽  
pp. 1293-1312 ◽  
Author(s):  
Tahreem Sahar ◽  
Aruna Nigam ◽  
Shadab Anjum ◽  
Farheen Waziri ◽  
Shipie Biswas ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Uterine Leiomyoma ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Differentially Expressed ◽  
Binding Motif ◽  
Differentially Expressed Proteins ◽  
Protein Patterns ◽  
Interacting Protein ◽  
Fatty Acid Binding

Background: Recent advances in proteomics present enormous opportunities to discover proteome related disparities and thus understanding the molecular mechanisms related to a disease. Uterine leiomyoma is a benign monoclonal tumor, located in the pelvic region, and affecting 40% of reproductive aged female. Objective: Identification and characterization of the differentially expressed proteins associated with leiomyogenesis by comparing uterine leiomyoma and normal myometrium. Methods: Paired samples of uterine leiomyoma and adjacent myometrium retrieved from twenty-five females suffering from uterine leiomyoma (n=50) were submitted to two-dimensional electrophoresis (2-DE), matrixassisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and to reverse transcription polymerase chain reaction (RT-PCR). Results: Comparison of protein patterns revealed seven proteins with concordantly increased spot intensities in leiomyoma samples. E3 ubiquitin-protein ligase MIB2 (MIB2), Mediator of RNA polymerase II transcription subunit 10 (MED10), HIRA-interacting protein (HIRP3) and Fatty acid binding protein brain (FABP7) were found to be upregulated. While, Biogenesis of lysosome-related organelles complex 1 subunit 2 (BL1S2), Shadow of prion protein (SPRN) and RNA binding motif protein X linked like 2 (RMXL2) were found to be exclusively present in leiomyoma sample. The expression modulations of the corresponding genes were further validated which corroborated with the 2-DE result showing significant upregulation in leiomyoma. We have generated a master network showing the interactions of the experimentally identified proteins with their close neighbors and further scrutinized the network to prioritize the routes leading to cell proliferation and tumorigenesis. Conclusion: This study highlights the importance of identified proteins as potential targets for therapeutic purpose. This work provides an insight into the mechanism underlying the overexpression of the proteins but warrants further investigations.

scholarly journals Synovial Sarcoma Translocation (SYT) Encodes a Nuclear Receptor Coactivator

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3892-3899 ◽  
Author(s):  
Toshiharu Iwasaki ◽  
Noriyuki Koibuchi ◽  
William W. Chin
Keyword(s):  
Synovial Sarcoma ◽  
Hormone Receptors ◽  
Rna Binding ◽  
Thyroid Hormone Receptor ◽  
Single Gene ◽  
Binding Motif ◽  
Dependent Manner ◽  
Interacting Protein ◽  
C Terminus ◽  
The Brain

Abstract We previously cloned and characterized a novel RNA-binding motif-containing coactivator, named coactivator activator (CoAA), as a thyroid hormone receptor-binding protein-interacting protein using a Sos-Ras yeast two-hybrid screening system. A database search revealed that CoAA is identical with synovial sarcoma translocation (SYT)-interacting protein. Thus, we hypothesized that SYT could also function as a coactivator. Subsequently, we isolated a cDNA encoding a larger isoform of SYT, SYT-long (SYT-L), from the brain and liver total RNA using RT-PCR. SYT-L possesses an additional 31 amino acids in its C terminus compared with SYT, suggesting that these two SYT isoforms may be expressed from two mRNAs produced by alternative splicing of a transcript from a single gene. By Northern blot analysis, we found that SYT-L mRNA is expressed in several human embryonic tissues, such as the brain, liver, and kidney. However, we could not detect SYT-L in adult tissues. Glutathione-S-transferase pull-down studies showed that SYT binds to the C-terminus of CoAA, but not to the coactivator modulator. Both isoforms of SYT function as transcriptional coactivators of nuclear hormone receptors in a ligand- and dose-dependent manner in CV-1, COS-1, and JEG-3 cells. However, the pattern of transactivation was different between SYT and SYT-L among these cells. SYT synergistically activates transcription with CoAA. In addition, SYT activates transcription through activator protein-1, suggesting that SYT may function as a general coactivator. These results indicate that SYT activates transcription, possibly through CoAA, to interact with the histone acetyltransferase complex.

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