Elucidating the role of FOXJ3 in regulating the expression of super enhancer associated KLF6 in kidney cancer cells / Che Muhammad Farhan Che Abdullah
Kidney cancer is one of the top ten most diagnosed cancers worldwide. Of that, clear cell renal cell carcinoma (ccRCC) accounts for 75% of kidney cancer and death cases. ccRCC is associated with a mutation in Von Hippel-Lindau (VHL) tumour suppressor genes that causes accumulation of hypoxia-indu...
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| Format: | Thesis |
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2022
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| Online Access: | http://studentsrepo.um.edu.my/14723/1/Che_Muhammad_Farhan.pdf http://studentsrepo.um.edu.my/14723/2/Che_Muhammad_Farhan.pdf http://studentsrepo.um.edu.my/14723/ |
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| Summary: | Kidney cancer is one of the top ten most diagnosed cancers worldwide. Of that, clear cell
renal cell carcinoma (ccRCC) accounts for 75% of kidney cancer and death cases. ccRCC
is associated with a mutation in Von Hippel-Lindau (VHL) tumour suppressor genes that
causes accumulation of hypoxia-inducible factor (HIF). The conventional strategy to treat
kidney cancer has been to target angiogenesis formation genes such as vascular
endothelial growth factor (VEGF) that are upregulated from the abundance of HIF.
Another target for kidney cancer treatment is the mechanistic target of rapamycin
(mTOR) pathway using mTOR inhibitors. However, the treatments remain ineffective
especially for patients with later stage cancers. Alternative therapeutic strategy for kidney
cancers is to look at its transcriptional machinery. A super enhancer associated gene,
Kruppel-like factor 6 (KLF6) has been identified as an important regulator in maintaining
kidney cancer cell growth and fitness. The transcription factors (TFs) that bind to the
super enhancer (SE) region near KLF6 has yet to be fully identified. Preliminary DNA
binding motif analysis has shown the transcription factor forkhead box J3 (FOXJ3) to be
one of the TFs that bind to this SE region. This project had designed a CRISPR
interference (CRISPRi) system targeting FOXJ3 in kidney cancer cell line, 786-M1A that
successfully showed a reduction of FOXJ3 expression. This in turn leads to a reduction
of KLF6 expression making FOXJ3 as one of the transcriptional machineries for KLF6.
The relationship between FOXJ3 and KLF6 provides the data for completing the picture
of the super enhancer assembly that drive KLF6 expression.
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