DOI
https://doi.org/10.25772/HMY9-WA97
Defense Date
2015
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Charles E. Chalfant, Ph.D.
Second Advisor
Margaret A. Park, Ph.D.
Third Advisor
Yue Sun, Ph.D.
Abstract
In the presented study, we identified that SRSF3 controls the alternative splicing of CPEB2 and consequently promotes a metastatic phenotype in triple negative breast cancer (TNBC). TNBC causes thousands of deaths annually, frequently due to a lack of effective treatments and a high rate of metastasis in patients. Alternative splicing has been found to be dysregulated in numerous cancers, while splicing factors such as SRSF3 are variably expressed. In this study we performed a siRNA panel to screen potential splicing factors, then used specific siRNA to study the effect of its knockdown on cellular function. These results showed that SRSF3 encourages the production of the pro-metastatic isoform of CPEB2, which contributes the aggressive phenotype of the tumor. We utilized numerous methods to measure the metastatic function of cultured TNBC cells to determine if SRSF3 strongly promoted the metastatic function. These data showed that siRNA reduction of SRSF3 was able to reduce the metastatic potential of cancer cells. These findings suggest that SRSF3 has great potential as a therapeutic measure to reduce and minimize the aggressiveness of TNBC tumors.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
8-5-2015