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“Discovery Of Gene Ripple Effect Which Causes Cervical Cancer to Advance And
Spread”May 19th, 2011
http://www.medicalnewstoday.com/releases/225831.php
Presentation By: Erica GreenDr. Ely
Biology 303August 25th, 2011
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Background Of News Article • Research Scientists at Cambridge University have
discovered that a common gene fault in cervical cancer
cells triggers a ripple of molecular signals, which makes
cervical cancer more aggressive.
• The scientist increased and decreased the activity of the
Drosha gene in cervical cancer cells.
• They also discovered that when Drosha is present in greater
quantities in cervical cancer cells that there is a change in
the production levels of microRNAs (miRNAs).
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Drosha Gene• Located on chromosome five.
• Is overabundant in the majority of advanced cervical cancer
tumors.
• Cells require this gene to make tiny cell signaling molecules
called miRNAs, which control the activity of hundreds of genes
vital to life.
• The changes in miRNAs levels can have the knock-on effect of
triggering unusual behavior in hundreds of important cell
signaling genes.
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MicroRNAs & Cancer
• MicroRNAs (miRNAs) are small, non-coding RNA molecules that
inhibit gene expression post-transcriptionally, resulting in either
the degradation or inhibition of translation of messengerRNA
(mRNA).
• Some miRNAs are thought to have oncogenic activity while
others have tumor suppressor activity; some miRNAs may
express either activity, depending on the situation and tissue
type.
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Cervical Cancer• Cancer that forms in tissues of the cervix.
The cells of the cervix become abnormal and start to grow uncontrollably, forming tumors.
• It’s almost always caused by human papillomavirus (HPV) infection.
• Most of the time, early cervical cancer has no symptoms.
• Benign growths (polyps, cysts, or genital warts).
• Malignant growths (cervical cancer).
• In the U.S., it is the fifth most common cancer among women aged 35-54, and the third most common cancer of the female reproductive tract.
• U.S. 2011 New cases:12,710 and Deaths:4,290.
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Journal Referenced
Functional evidence that Drosha overexpression in
cervical squamous cell carcinoma affects cell
phenotype and microRNA profiles
Muralidhar et al.
Article published May 18th, 2011
In
The Journal of Pathology
Volume 224, Issue 4, pages 496-507, August 2011
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Introduction Key Points
• They demonstrated that Drosha copy-number gain and overexpression occur
frequently in cervical squamous cell carcinoma (SCC) samples and cell lines, and are
associated with substantial differences in microRNA profiles, with increased levels
of some microRNAs (the most significant being miR-31) and decreased levels of
others.
• Interestingly, Drosha overexpression in SCC of the esophagus correlates with
metastasis and adverse survival, independently of tumor stage.
• They demonstrate, using gene depletion/overexpression experiments, that
alteration of Drosha levels in cervical SCC cells causes significant changes in cell
phenotype in vitro and differential expression of key microRNAs.
• Their data provides direct experimental evidence of the significance of Drosha
overexpression in advanced cervical SCC.
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Hierarchical clustering of global microRNA profiles in cervical SCC cells based on all 319
microRNAs on the array.
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Discussion Key Points • Together, these experimental data indicate that Drosha may
represent an important oncogene in cervical and potentially other
SCCs.
• Though Drosha is not the sole determinate of the phenotypes
observed, findings do indicate that in cervical SCC cells where Drosha
is overexpressed, the protein makes a significant contribution to cell
motility/ invasion, via altered expression of cancer-related microRNAs
that can affect large numbers of protein coding genes.
• Future goal: Defining the role of specific microRNAs in cervical
carcinogenesis, such as miR-31.