scholarly journals The diagnostic performance of serum LIM homeobox transcription factor 1 alpha in patients with gastric cancer

Medicine ◽  
2019 ◽  
Vol 98 (22) ◽  
pp. e15783
Author(s):  
Dinuo Li ◽  
Chen Li
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Diagnostic Performance ◽  
Homeobox Transcription Factor ◽  
Transcription Factor 1

scholarly journals Lmx1b influences correct post-mitotic coding of mesodiencephalic dopaminergic neurons

2018 ◽  
Author(s):  
Iris Wever ◽  
Pablo Largo Barrientos ◽  
Elisa J. Hoekstra ◽  
Marten P. Smidt
Keyword(s):  
Transcription Factor ◽  
Dopaminergic Neurons ◽  
Cell Types ◽  
Late Development ◽  
Genetic Ablation ◽  
Depth Analysis ◽  
Homeobox Transcription Factor ◽  
Different Cell Types ◽  
Transcription Factor 1 ◽  
Inductive Activity

AbstractThe Lim Homeobox transcription factor 1 beta (LMX1b) has been identified as one of the transcription factors important for the development of mesodiencephalic dopaminergic (mdDA) neurons. During early development, Lmx1b is essential for induction and maintenance of the Isthmic Organizer (IsO), and genetic ablation results in the disruption of inductive activity from the IsO and loss of properly differentiated mdDA neurons.To study the downstream targets of Lmx1b without affecting the IsO, we generated a conditional model in which Lmx1b was selectively deleted in Pitx3 expressing cells from embryonic day (E)13 onward. Supporting previous data, no significant changes could be observed in general dopamine (DA) marks, like Th, Pitx3 and Vmat2 at E14.5. However, in depth analysis by means of RNA-sequencing revealed that Lmx1b is important for the expression level of survival factors En1 and En2 and for the repression of mdDA subset mark Ahd2 during (late) development. Interestingly, the regulation of Ahd2 by Lmx1b was found to be Pitx3 independent, since Pitx3 levels were not altered in Lmx1b conditional knock-outs (cKO) and Ahd2 expression was also up-regulated in Lmx1b/Pitx3 double mutants compared to Pitx3 mutants. Further analysis of Lmx1b cKOs showed that post-mitotic deletion of Lmx1b additional leads to a loss of TH+ cells at 3 months age both in the VTA and SNc. Remarkably, different cell types were affected in the SNc and the VTA. While TH+AHD2+ cells were lost the SNc, TH+AHD2- neurons were affected in the VTA, reflected by a loss of Cck expression, indicating that Lmx1b is important for the survival of a sub-group of mdDA neurons.

scholarly journals Bcl-2-associated transcription factor 1 Ser290 phosphorylation mediates DNA damage response and regulates radiosensitivity in gastric cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jia Liu ◽  
Jingyi Li ◽  
Zhao Sun ◽  
Yangmiao Duan ◽  
Fengqin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Damage ◽  
Transcription Factor ◽  
Protein Phosphorylation ◽  
Dna Damage Response ◽  
High Resolution Mass Spectrometry ◽  
Gene Set Enrichment Analysis ◽  
Label Free ◽  
Damage Response ◽  
Transcription Factor 1

Abstract Background DNA damage response plays critical roles in tumor pathogenesis and radiotherapy resistance. Protein phosphorylation is a critical mechanism in regulation of DNA damage response; however, the key mediators for radiosensitivity in gastric cancer still needs further exploration. Methods A quick label-free phosphoproteomics using high-resolution mass spectrometry and an open search approach was applied to paired tumor and adjacent tissues from five patients with gastric cancer. The dysregulated phosphoproteins were identified and their associated-pathways analyzed using Gene Set Enrichment Analysis (GSEA). The mostly regulated phosphoproteins and their potential functions were validated by the specific antibodies against the phosphorylation sites. Specific protein phosphorylation was further analyzed by functional and clinical approaches. Results 832 gastric cancer-associated unique phosphorylated sites were identified, among which 25 were up- and 52 down-regulated. Markedly, the dysregulated phosphoproteins were primarily enriched in DNA-damage-response-associated pathways. Particularly, the phosphorylation of Bcl-2-associated transcription factor 1 (BCLAF1) at Ser290 was significantly upregulated in tumor. The upregulation of BCLAF1 Ser290 phosphorylation (pBCLAF1 (Ser290)) in tumor was confirmed by tissue microarray studies and further indicated in association with poor prognosis of gastric cancer patients. Eliminating the phosphorylation of BCLAF1 at Ser290 suppressed gastric cancer (GC) cell proliferation. Upregulation of pBCLAF1 (Ser290) was found in association with irradiation-induced γ-H2AX expression in the nucleus, leading to an increased DNA damage repair response, and a marked inhibition of irradiation-induced cancer cell apoptosis. Conclusions The phosphorylation of BCLAF1 at Ser290 is involved in the regulation of DNA damage response, indicating an important target for the resistance of radiotherapy.

scholarly journals Bcl-2-associated Transcription Factor 1 Phosphorylation Mediated DNA Damage Response in Gastric Cancer

2021 ◽  
Author(s):  
Jia Liu ◽  
Jingyi Li ◽  
Zhao Sun ◽  
Yangmiao Duan ◽  
Fengqin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Damage ◽  
Transcription Factor ◽  
Protein Phosphorylation ◽  
Dna Damage Response ◽  
High Resolution Mass Spectrometry ◽  
Gene Set Enrichment Analysis ◽  
Label Free ◽  
Damage Response ◽  
Transcription Factor 1

Abstract Background: DNA damage response plays critical roles in tumor pathogenesis and radiotherapy resistance. Various cellular activities including the initiation and major steps DNA damage response are regulated by protein phosphorylation, whereas the molecular mechanism remains largely unknown. Methods: A quick label-free phosphoproteomics using high-resolution mass spectrometry and an open search approach was applied to paired tumor and adjacent tissues from five patients with gastric cancer. The dysregulated phosphoproteins were identified and their associated-pathways analyzed using Gene Set Enrichment Analysis (GSEA). The mostly regulated phosphoproteins and their potential functions were validated by the specific antibodies against the phosphorylation sites. Specific protein phosphorylation was further analyzed by functional and clinical approaches. Results: 832 gastric cancer-associated unique phosphorylated sites were identified, among which 25 were up- and 52 down-regulated. Markedly, the dysregulated phosphoproteins were primarily enriched in DNA-damage-response-associated pathways. Particularly, the phosphorylation of Bcl-2-associated transcription factor 1 (BCLAF1) at Ser290 was significantly upregulated in tumor. The upregulation of BCLAF1 Ser290 phosphorylation (pBCLAF1(Ser290)) in tumor was confirmed by tissue microarray studies and further indicated in association with poor prognosis of gastric cancer patients. Eliminating the phosphorylation of BCLAF1 at Ser290 suppressed gastric cancer (GC) cell proliferation. Upregulation of pBCLAF1(Ser290) was found in association with irradiation-induced γ-H2AX expression in the nucleus, leading to an increased DNA damage repair response, and a marked inhibition of irradiation-induced cancer cell apoptosis. Conclusions: The phosphorylation of BCLAF1 at Ser290 is involved in the regulation of DNA damage response, indicating an important target for the resistance of radiotherapy.

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