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Dr. MIKHLID HAMMAD ALMUTAIRI د. مخلد بن حامد المطيري

Associate Professor

Faculty member in Molecular Genetics

كلية العلوم
College of Sciences No. 5, ground floor, Office No. AB 67
المنشورات
مقال فى مجلة
2017
تم النشر فى:

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

McFarlane, Vicente Planells-Palop, Ali Hazazi, Julia Feichtinger, Jana Jezkova, Gerhard Thallinger, Naif O. Alsiwiehri, Mikhlid Almutairi, Lee Parry, Jane A. Wakeman and Ramsay J. . 2017

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.

رقم المجلد
16
رقم الانشاء
84
مجلة/صحيفة
Molecular Cancer
الصفحات
1-18
مزيد من المنشورات
publications

The tumor suppressor gene TP53 and its downstream genes P21 and MDM2 play crucial roles in combating DNA damage at the G1/S cell cycle checkpoint. Polymorphisms in these genes can lead to the…

بواسطة Mikhlid H. Almutairi , Bader O. Almutairi , Turki M. Alrubie, Sultan N. Alharbi, Narasimha R. Parine, Abdulwahed F. Alrefaei, Ibrahim Aldeailej, Abdullah Alamri, Abdelhabib Semlali
2021
publications

Background: Tumor suppresser gene (TP53) and its downstream genes (P21 and MDM2) play crucial roles in the regulation of DNA damage checkpoint (G1/S) of the cell cycle. Genetic polymorphisms in…

2019