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

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