Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by the TBX2 Subfamily of Tumor Suppressor Genes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA509770 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR8315060_1.fastq.gz | Fastqsanger.gz | |||
| SRR8315060_2.fastq.gz | Fastqsanger.gz | |||
| SRR8315070_1.fastq.gz | Fastqsanger.gz | |||
| SRR8315070_2.fastq.gz | Fastqsanger.gz | |||
| SRR8315061_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 36 |
Similar Datasets
Project description:T-box (TBX) transcription factors are evolutionary conserved genes and master transcriptional regulators. In mammals, TBX2 subfamily (TBX2, TBX3, TBX4, and TBX5) genes are expressed in the developing lung bud and tracheae. Our group previously showed that the expression of TBX2 subfamily was significantly high in human normal lungs, but markedly suppressed in lung adenocarcinoma (LUAD). To further elucidate their role in LUAD pathogenesis, we first confirmed abundant expression of protein products of the four members by immunostaining in adult human normal lung tissues. We also found overall suppressed expression of these genes and their corresponding proteins in a panel of human LUAD cell lines. Transient over-expression of each of the genes in human (NCI-H1299), and mouse (MDA-F471) derived lung cancer cells was found to significantly inhibit growth and proliferation as well as induce apoptosis. Genome-wide transcriptomic analyses on NCI-H1299 cells, overexpressing TBX2 gene subfamily, unraveled novel regulatory pathways. These included, among others, inhibition of cell cycle progression but more importantly activation of the histone demethylase pathway. When using a pattern-matching algorithm, we showed that TBX's overexpression mimic molecular signatures from azacitidine treated NCI-H1299 cells which in turn are inversely correlated to expression profiles of both human and murine lung tumors relative to matched normal lung. In conclusion, we showed that the TBX2 subfamily genes play a critical tumor suppressor role in lung cancer pathogenesis through regulating its methylating pattern, making them putative candidates for epigenetic therapy in LUAD.
2018-12-14 | GSE123769 | GEO
Project description:T-box (TBX) transcription factors are evolutionary conserved genes and master transcriptional regulators. In mammals, TBX2 subfamily (TBX2, TBX3, TBX4, and TBX5) genes are expressed in the developing lung bud and tracheae. Our group previously showed that the expression of TBX2 subfamily was significantly high in human normal lungs, but markedly suppressed in lung adenocarcinoma (LUAD). To further elucidate their role in LUAD pathogenesis, we first confirmed abundant expression of protein products of the four members by immunostaining in adult human normal lung tissues. We also found overall suppressed expression of these genes and their corresponding proteins in a panel of human LUAD cell lines. Transient over-expression of each of the genes in human (NCI-H1299), and mouse (MDA-F471) derived lung cancer cells was found to significantly inhibit growth and proliferation as well as induce apoptosis. Genome-wide transcriptomic analyses on NCI-H1299 cells, overexpressing TBX2 gene subfamily, unraveled novel regulatory pathways. These included, among others, inhibition of cell cycle progression but more importantly activation of the histone demethylase pathway. When using a pattern-matching algorithm, we showed that TBX's overexpression mimic molecular signatures from azacitidine treated NCI-H1299 cells which in turn are inversely correlated to expression profiles of both human and murine lung tumors relative to matched normal lung. In conclusion, we showed that the TBX2 subfamily genes play a critical tumor suppressor role in lung cancer pathogenesis through regulating its methylating pattern, making them putative candidates for epigenetic therapy in LUAD.
| S-EPMC6218583 | biostudies-literature
Project description:Despite being found in the notochord of several chordates, the roles of the Tbx2 subfamily of T-box transcription factors in the development of this tissue remain largely unknown. We explored the targets of the only Tbx2 subfamily member in Ciona intestinalis, Ci-Tbx2/3, by expressing mutant forms of the transcriptional regulator using the Ci-Bra promoter region. We produced a dominant interfering version of Ci-Tbx2/3 (Tbx2/3DBD) through expression of a truncated version consisting only of its DNA-binding domain (DBD) and a constitutive activator form by attaching the T-box of Ci-Tbx2/3 to the VP16 transactivation domain (Tbx2/3VP16). These constructs were introduced into 1-cell stage embryos and grown to the neurula (N) or mid-tailbud (mTb) stage to capture targets regulated throughout notochord morphogenesis. Ci-Tbx2/3 targets were ascertained using whole-genome custom Affymetrix microarrays to compare the transcription levels of Tbx2/3DBD and Tbx2/3VP16 expressing embryos to wild-type controls (Bra>GFP) at the neurula or mTb stages.
2013-04-27 | E-GEOD-42267 | biostudies-arrayexpress
Project description:Despite being found in the notochord of several chordates, the roles of the Tbx2 subfamily of T-box transcription factors in the development of this tissue remain largely unknown. We explored the targets of the only Tbx2 subfamily member in Ciona intestinalis, Ci-Tbx2/3, by expressing mutant forms of the transcriptional regulator using the Ci-Bra promoter region. We produced a dominant interfering version of Ci-Tbx2/3 (Tbx2/3DBD) through expression of a truncated version consisting only of its DNA-binding domain (DBD) and a constitutive activator form by attaching the T-box of Ci-Tbx2/3 to the VP16 transactivation domain (Tbx2/3VP16). These constructs were introduced into 1-cell stage embryos and grown to the neurula (N) or mid-tailbud (mTb) stage to capture targets regulated throughout notochord morphogenesis.
2013-04-27 | GSE42267 | GEO
Project description:We report the high-throughput profiling of Tbx2 binding sites in mouse melanoma B16 cells. We generated B16 clones that have endogenous Tbx2 tagged with 3xHA, and used HA antibody for immunoprecipitation. This study provides a high-quality genome-wide Tbx2 binding profile and helps further understand Tbx2 role in melanoma progression
2022-01-07 | GSE175703 | GEO
Project description:RNA-seq upon TBX2 knockdown in the neuroblastoma cell line CLB-GA. Cells were transduced with two different shRNAs (sh#2 and sh#4) targeting TBX2 and a non-targeting control (NTC), and selected with puromycin. Analysis was performed seven days upon TBX2 knockdown, including three biological replicates per condition.
2018-08-16 | E-MTAB-6567 | biostudies-arrayexpress
Project description:Here we demonstrate a previously unknown mechanism of TBX2-mediated gene repression in breast tumours, whereby TBX2 physically interacts with CoREST-associated proteins LSD1, HDAC1 and the ZNF217 oncogene. Through Chromatin Immunoprecipitation sequencing (ChIP-seq) we find that while over 80% of TBX2 binding sites are concentrated at promoters, these regions show remarkably no enrichment for the T-box element; rather TBX2-bound regions are biased toward a small number of non-T-box motifs, with the most abundant being Specificity Protein 1 (Sp1), EGR1 and Nuclear Transcription Factor Y (NF-Y). Furthermore, we uncover that Sp1 is crucial for recruitment of TBX2 to the NDRG1 promoter and subsequent repression of this gene. We also observe that ZNF217 cooccupies approximately 30% of TBX2-bound sites, a number of which contain RCOR1 and exhibit upregulation of the associated transcripts following disruption of TBX2/CoREST function. Overall these data highlight a novel potential therapeutic opportunity whereby poor-prognosis, TBX2 overexpressing breast tumours may be pharmacologically exploited by targeting the CoREST-dependent gene repression network, to recover normal growth control.
2022-05-23 | GSE180213 | GEO
Project description:Atoh1 is essential for the development of both outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas Ikzf2 is necessary for OHC development, the key gene required for IHC development remains unknown. We found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes, including Ikzf2. More importantly, persistent expression of Tbx2 coupled with transient Atoh1 expression effectively reprogramed non-sensory supporting cells into new IHCs expressing the functional IHC marker vGlut3. The differentiation status of these new IHCs was considerably more advanced than that previously reported. Thus, Tbx2 is essential for IHC development, and co-upregulation of Tbx2 with Atoh1 in supporting cells represents a new approach for treating deafness related to IHC degeneration.
2022-08-09 | GSE199369 | GEO
Project description:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. The lack of access to human myometrial samples during ongoing uncomplicated pregnancy seriously hampers proper understanding of the sequence of events leading to parturition initiation. In our previous work we used mouse as a model and profiled gene expression in mouse uterus from early E6.5 to late gestation E17.5. We identified Tbx2 as one of the putative upstream regulators during mid-gestation (E10.5, E12.5, E15.5). The role of TBX2 in human myometrium has not been investigated. In this study we identify the gene targets of TBX2 by overexpressing TBX2 in cultured telomerase immortalised myometrial cells followed by gene expression profiling using microarrays.
2021-04-29 | GSE134446 | GEO
Project description:RNA-seq upon TBX2, MYCN or combination of TBX2 and MYCN knockdown in the neuroblastoma cell line IMR-5/75. Cells were transduced with two different shRNAs (shTBX2_2 and shTBX2_4) targeting TBX2 and a non-targeting control (NTC), and selected with puromycin. Cells were treated with doxycycline for shMYCN induction (with DOX or not). Analysis was performed three days upon TBX2 knockdown and two days upon MYCN knockdown, including six biological replicates per condition.
2018-08-16 | E-MTAB-6568 | biostudies-arrayexpress