scholarly journals Over-expression of Hsp83 in grossly depleted hsrω lncRNA background causes synthetic lethality and l(2)gl phenocopy in Drosophila

2018 ◽  
Author(s):  
Mukulika Ray ◽  
Sundaram Acharya ◽  
Sakshi Shambhavi ◽  
Subhash C. Lakhotia
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Rna Sequencing ◽  
Synthetic Lethality ◽  
Suppressor Gene ◽  
Gene Promoters ◽  
Larval Life ◽  
Over Expression ◽  
Regulatory Circuits ◽  
Omega Speckles

AbstractWe examined interactions between Hsp83 and hsrω lncRNAs in hsrω66Hsp90GFP homozygotes, which almost completely lack hsrω lncRNAs but over-express Hsp83. All +/+; hsrω66Hsp90GFP progeny died before third instar. Rare Sp/CyO; hsrω66Hsp90GFP reached third instar stage but phenocopied l(2)gl mutants, dying after prolonged larval life, becoming progressively bulbous and transparent with enlarged brain. Additionally, ventral ganglia were elongated. However, hsrω66Hsp90GFP/TM6B heterozygotes, carrying +/+ or Sp/CyO second chromosomes, developed normally. Total RNA sequencing (+/+, +/+; hsrω66/hsrω66, Sp/CyO; hsrω66/hsrω66, +/+; Hsp90GFP/Hsp90GFP, and Sp/CyO; hsrω66Hsp90GFP/hsrω66Hsp90GFP late third instar larvae) revealed similar effects on many genes in hsrω66 and Hsp90GFP homozygotes. Besides additive effect on many of them, numerous additional genes were affected in Sp/CyO; hsrω66Hsp90GFP larvae, with l(2)gl and several genes regulating CNS being highly down-regulated in surviving Sp/CyO; hsrω66Hsp90GFP larvae, but not in hsrω66 or Hsp90GFP single mutants. Hsp83 binds at these gene promoters. Several omega speckle associated hnRNPs too may bind with these genes and transcripts. Hsp83-hnRNP interactions are also known. Thus, elevated Hsp83 in altered hnRNP distribution and dynamics, following absence of hsrω lncRNAs and omega speckles, background can severely perturb regulatory circuits with unexpected consequences, including down-regulation of tumor suppressor gene like l(2)gl.

scholarly journals Quantitative Methylation Profiles for Multiple Tumor Suppressor Gene Promoters in Salivary Gland Tumors

PLoS ONE ◽  
2010 ◽  
Vol 5 (5) ◽  
pp. e10828 ◽  
Author(s):  
Megan L. Durr ◽  
Wojciech K. Mydlarz ◽  
Chunbo Shao ◽  
Marianna L. Zahurak ◽  
Alice Y. Chuang ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Salivary Gland Tumors ◽  
Gene Promoters ◽  
Multiple Tumor

scholarly journals MYCN Amplification and ATRX Mutations are Incompatible in Neuroblastoma

2018 ◽  
Author(s):  
Maged Zeineldin ◽  
Sara Federico ◽  
Xiang Chen ◽  
Yiping Fan ◽  
Beisi Xu ◽  
...  
Keyword(s):  
High Risk ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Synthetic Lethality ◽  
Reactive Oxygen Species Generation ◽  
Suppressor Gene ◽  
Metabolic Reprogramming ◽  
Mycn Amplification ◽  
Replicative Stress ◽  
Chaperone Complex

SUMMARYAggressive cancers often have activating mutations in growth-controlling oncogenes and inactivating mutations in tumor-suppressor genes. In neuroblastoma, amplification of the MYCN oncogene and inactivation of the ATRX tumor-suppressor gene correlate with high-risk disease and poor prognosis. Here we show that ATRX mutations and MYCN amplification are mutually exclusive across all ages and stages in neuroblastoma. Using human cell lines and mouse models, we found that elevated MYCN expression and ATRX mutations are incompatible. Elevated MYCN levels promote metabolic reprogramming, mitochondrial dysfunction, reactive-oxygen species generation, and DNA-replicative stress. The combination of replicative stress caused by defects in the ATRX–histone chaperone complex and that induced by MYCN-mediated metabolic reprogramming leads to synthetic lethality. Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.

scholarly journals Corepressor CtBP and Nuclear Speckle Protein Pnn/DRS Differentially Modulate Transcription and Splicing of the E-Cadherin Gene

2007 ◽  
Vol 28 (5) ◽  
pp. 1584-1595 ◽  
Author(s):  
Roman Alpatov ◽  
Yujiang Shi ◽  
Gustavo C. Munguba ◽  
Babak Moghimi ◽  
Jeong-Hoon Joo ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Molecular Switches ◽  
Suppressor Gene ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Gene Promoters ◽  
Nuclear Speckle ◽  
Tumorigenic Potential ◽  
E Cadherin

ABSTRACT CtBP is a transcriptional corepressor with tumorigenic potential that targets the promoter of the tumor suppressor gene E-cadherin. Pnn/DRS (Pnn) is a “nuclear speckle”-associated protein involved in mRNA processing as well as transcriptional regulation of E-cadherin via its binding to CtBP. Here, we show that CtBP can recruit Pnn to CtBP-associated complexes, resulting in Pnn-dependent chromatin remodeling at the E-cadherin promoter. In addition, CtBP and Pnn can differentially modulate E-cadherin mRNA splicing, with polymerase II serving as an interface in this event. Therefore, the Pnn/CtBP functional interplay represents a novel mechanism linking the corepressor CtBP and Pnn to the transcription-coupled mRNA splicing of a major tumor suppressor gene. Our findings implicate the existence of the molecular switches involved in tumorigenesis, which coordinate promoter-specific events and mRNA processing, by serving as bridging elements between the regulatory complexes both at gene promoters and within the mRNA splicing machineries.

Abstract 4929: Hypermethylation of tumor suppressor gene promoters in basal cell carcinoma

2010 ◽  
Author(s):  
Tjinta Brinkhuizen ◽  
Manon van Engeland ◽  
Ariënne van Marion ◽  
Maurice van Steensel
Keyword(s):  
Tumor Suppressor ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Suppressor Gene ◽  
Basal Cell ◽  
Suppressor Gene ◽  
Gene Promoters

scholarly journals Methylation pattern of tumor-suppressor gene promoters as putative noninvasive diagnostic markers for prostate cancer

2021 ◽  
Vol 37 (1) ◽  
pp. 23-32
Author(s):  
O. S. Mankovska ◽  
A. S. Korsakova ◽  
K. R. Cherniavskyi ◽  
O. A. Kononenko ◽  
E. O. Stakhovskyy ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Methylation Pattern ◽  
Diagnostic Markers ◽  
Gene Promoters

Remodeling epigenetic modifications at tumor suppressor gene promoters with bovine oocyte extract

Cytotherapy ◽  
2013 ◽  
Vol 15 (9) ◽  
pp. 1164-1173 ◽  
Author(s):  
Zhenfei Wang ◽  
Yongli Yue ◽  
Pengyong Han ◽  
Rula Sa ◽  
Xiaolv Ren ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Epigenetic Modifications ◽  
Gene Promoters ◽  
Bovine Oocyte
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