علي محمد أحمد هزازي

 


      
 
الاسم الاول: 
علي
اسم العائلة: 
هزازي
الدرجة العلمية: 
دكتوراة
مجال الدراسة: 
الطب و الخدمات الصحية
المؤسسة التعليمية: 
Bangor University

مجال التميز

تميز دراسي و بحثي

 

 

البحوث المنشورة

 

البحث (1):

 

عنوان البحث:

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis 

رابط إلى البحث:

Click Here  

تاريخ النشر:

   26/04/2017

موجز عن البحث:

Background

Cancer/testis (CT) genes have expression normally restricted to the testis, but become activated during oncogenesis, so they have excellent potential as cancer-specific biomarkers. Evidence is starting to emerge to indicate that they also provide function(s) in the oncogenic programme. Human TEX19 is a recently identified CT gene, but a functional role for TEX19 in cancer has not yet been defined.

Methods

siRNA was used to deplete TEX19 levels in various cancer cell lines. This was extended using shRNA to deplete TEX19 in vivo. Western blotting, fluorescence activated cell sorting and immunofluorescence were used to study the effect of TEX19 depletion in cancer cells and to localize TEX19 in normal testis and cancer cells/tissues. RT-qPCR and RNA sequencing were employed to determine the changes to the transcriptome of cancer cells depleted for TEX19 and Kaplan-Meier plots were generated to explore the relationship between TEX19 expression and prognosis for a range of cancer types.

Results

Depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. Analysis of cells depleted for TEX19 indicates they enter a quiescent-like state and have subtle defects in S-phase progression. TEX19 is present in both the nucleus and cytoplasm in both cancerous cells and normal testis. In cancer cells, localization switches in a context-dependent fashion. Transcriptome analysis of TEX19 depleted cells reveals altered transcript levels of a number of cancer-/proliferation-associated genes, suggesting that TEX19 could control oncogenic proliferation via a transcript/transcription regulation pathway. Finally, overall survival analysis of high verses low TEX19 expressing tumours indicates that TEX19 expression is linked to prognostic outcomes in different tumour types.

Conclusions

TEX19 is required to drive cell proliferation in a range of cancer cell types, possibly mediated via an oncogenic transcript regulation mechanism. TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

 

 

 

المؤتمرات العلمية:

 

 

 

المؤتمر (1):

 

عنوان المؤتمر:

2nd EACR-OECI Conference. Making it Personal: Cancer Precision Medicine

تاريخ الإنعقاد:

13-16/03/2017

مكان الإنعقاد:

Amsterdam, Netherlands

طبيعة المشاركة:

Poster presentation

عنوان المشاركة:

Human germ/stem cell-specific gene TEX19 influences cancer cell proliferation and cancer prognosis

 

ملخص المشاركة:

Tumours regularly reactivate germ line genes whose expression is silenced in normal healthy somatic tissues and restricted to the tissues of the testis. These genes are found to be expressed in a wide range of tumour cells and cancer stem-like cells, so their intrinsic characteristics mark them as excellent potential cancer-specific biomarkers and a promising therapeutic target. Human TEX19 is a germ line gene that has a yet to have a functional role in oncogenesis defined. Here we demonstrate that depletion of TEX19 levels in a range of cancer cell lines in vitro and in vivo restricts cellular proliferation/self-renewal/reduces tumour volume, indicating TEX19 is required for cancer cell proliferative/self-renewal potential. We extend this to show that TEX19 has a dynamic cellular localisation pattern. We also show that TEX19 expression is linked to a poor prognosis for some cancers and collectively these findings indicate that not only can TEX19 expression serve as a novel cancer biomarker, but may also offer a cancer-specific therapeutic target with broad spectrum potential.

 

 

 

المرفقالحجم
Making it Personal 2017 conference participation.pdf‏144.25 ك.بايت