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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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Location of Drosha gene: 5p13.3

-chromosome 5

-short arm

-region #1

-band #3

-sub-band #3

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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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Effects of Drosha depletion on cervical SCC cell migration in vitro.

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Cont.

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Effects of Drosha depletion on cervical SCC cell invasion in vitro.

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Phenotype rescue of the effects of Drosha depletion on SW756 cell invasion

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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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Hierarchical clustering based on the 45 differentially expressed microRNAs.

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miR-31 expression levels in cervical SCC cell lines.

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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.

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Why I Chose This Article?

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Any Questions, Comments, or Suggestions?

Thanks for listening!