Regulation of Genes
We are investigating the role of developmental proteins (e.g., HOXA10) in regulation of tumor suppressors (e.g. p53) to identify the molecular mechanisms fueling metastasis in breast cancer. The study reveals novel therapeutic targets for drug industry to fight against the leading cause of cancer deaths in Pakistan. Epigenetic silencing of tumor suppressors by chromatin remodeling proteins like CTCF is an active area to find potential locations for gene therapy in cancers. In another front we have established a functional relationship of CFTR gene with male infertility disease CBAVD and working to unveil the signaling cascades involved in disease onset.
CTCF knock down dependent expression of p53 results in cancer cell death by isolating cancer cell from the surrounding with decreased ITGB4 expression
Theme (Mustafa et.al., J Cancer 2017; 8(11):2124-2131)
Figure S6. Expression and localization of ITGB4 in MCF-7 cells. (A) mRNA expression level of ITGB4 and CTCF in control non-specific (Control-NS) and CTCF-knockdown (CTCF-KD) cells. (B) Confocal microscopy images showing ITGB4 and p53 in Control-NS and CTCF-KD cells. Antibodies against p53 (sc-126; Santa Cruz,), ITGB4 (ab133682; Abcam) and the corresponding secondary antibodies (anti-rabbit IgG Alexa Flour 594 and anti-goat IgG Alexa Flour 488; Invitrogen) were used for detection. Cells were counterstained with DAPI (Invitrogen) and analyzed using a Zeiss LSM700 confocal microscope.Zoomed images of square boxes in c and g are shown in i-l and m-p, respectively.
CTCF is a Transcriptional inhibitor of HOXA10 as well as p53, it binds directly to the promoter region of these two tumor suppressors, interferes with RNA pol II and supports the recruitment of inactive epigenetic markers at the promoter region. Cancer cell use higher levels of CTCF to turn off these critical tumor suppressors to promote their survival and proliferation.
Rimsha Farooq . Khadim Hussain . Muhammad Tariq . Ali Farooq and Muhammad Mustafa CRISPR/Cas9: targeted genome editing for the treatment of hereditary hearing loss (J Appl Genetics, 2020. https://doi.org/10.1007/s13353-019-00535-6)
Muhammad Mustafa, Ji-Yeon Lee, Clara Yuri Kim and Myoung Hee Kim. Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53 (J Cancer, 2017) Full Text
Muhammad Mustafa, Ji-Yeon Lee and Myoung Hee Kim CTCF negatively regulates HOXA10 expression in breast cancer cell lines (BBRC, 2015) Full Text
Muhammad Mustafa, Ji-Yeon Lee and Myoung Hee Kim CTCF regulates HOXA10 expression in breast cancer cell lines (the FEBS Journal (Special Issue) Volume 282 Supplement 1 Page 60, July 2015)
Abdul Rauf1, Muhammad Shahid Nadeem1, Akbar Ali1, Muhammad Iqbal1, Muhammad Mustafa1,Muhammad Muzammal Latif1, Muhammad Zahid Latif2, Nisar Ahmed3 and Abdul Rauf Shakoori1.Prevalence of hepatitis B and C in internally displaced persons of war against terrorism in Swat, Pakistan Eur J Public Health 21(5) 638-42 2011
M.S. Nadeem, A. Rauf, M. Mustafa., M. Iqbal and A.R. Shakoori. 2010.Selective precipitation based economical methods for purification of Human Serum Albumin from the out-dated blood bank samples. Pakistan Journal of Zoology 42(4), pp. 498-501.
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