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Thesis Format

Monograph

Degree

Master of Science

Program

Pathology and Laboratory Medicine

Supervisor

Min, Weiping

Abstract

Prostate cancer (PCa) is the third leading cause of cancer mortality in Canadian males, highlighting a need for continued research in this area. We have previously found that circHUWE1 is upregulated in highly metastatic PCa cells. Therefore, we hypothesized that circHUWE1 promotes PCa cell proliferation, migration, and invasion. PC-3 cells were transfected with circHUWE1 siRNA to perform loss-of-function experiments. Knockdown of circHUWE1 significantly reduced cell proliferation and migration. mRNA expressions of multiple proliferation-related genes were affected: HMGA1, CDK6, and HDAC2 were significantly increased, while P21 and CCND1 were significantly decreased. A significant reduction in vimentin protein expression was observed, suggesting circHUWE1 promotes epithelial-to-mesenchymal transition. Additionally, knockdown of circHUWE1 significantly reduced RAC1 and MAPK1 mRNA expression, suggesting circHUWE1 may exert its effects through these molecules. Understanding the role of circHUWE1 in PCa may contribute to the development of targeted therapeutics to improve outcomes for patients with metastatic prostate cancer.

Summary for Lay Audience

Prostate cancer is the most common type of cancer and third most common cause of cancer death in Canadian males. Prostate cancer is usually treatable. However, after the cancer has spread to different areas in the body, the survival rate of people with prostate cancer significantly decreases. Therefore, this research aims to identify a new molecule that is involved in prostate cancer progression that could be targeted in the future for the development of new treatment options.

We previously found that a molecule called circular RNA HUWE1 (circHUWE1) is highly expressed in prostate cancer that has spread throughout the body. Based on this, we believe that circHUWE1 may have a role in prostate cancer progression. Thus, this research aimed to understand how circHUWE1 may affect prostate cancer.

To do this, we decreased the levels of circHUWE1 in prostate cancer cells. We then examined the changes in the growth and spread of the cells with lower levels of circHUWE1 compared to normal prostate cancer cells. We also looked at other molecules related to cell growth and cell spread to explain how circHUWE1 affects prostate cancer.

We found that prostate cancer cells with lower levels of circHUWE1 had less cell growth and cell migration compared to normal prostate cancer cells. We also found that reducing the levels of circHUWE1 in prostate cancer cells affected the activity levels of other genes that were related to cell growth and spread. Additionally, we found that reducing circHUWE1 levels led to a reduction in the levels of two molecules called RAC1 and MAPK1. Therefore, we believe that circHUWE1 may promote the progression of prostate cancer through these molecules.

This research helps us to understand the biology of prostate cancer. It also identifies a new molecule involved in prostate cancer that could be used in future treatments to improve survival rates of people whose prostate cancer has spread to different areas of the body.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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