蘇怡媛

Hello, my name is Yi-Yuan (Wendy) Su. I have a Master's degree in Biological Science and Technology from NYCU, and I am currently pursuing a doctoral degree in the same field. My primary research interest is to explore the pathogenic mechanisms of cancer. Specifically, I am studying the impact of the RNA helicase, DEAD-box helicase 3 X-linked (DDX3X), on the functionality of exosomes in hepatocellular carcinoma (HCC). My goal is to contribute to the development of novel therapeutic strategies for cancer patients.

DDX3 Inhibits the Progression of Hepatocellular Carcinoma by Regulating the Exosomes Secretion

Yi-Yuan Su (蘇怡媛)1,2, Hsiang-Yu Hsu2,3, Yan-Hwa Wu Lee1,2, and Ru-Tsun Mai1,2

1Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University

2 Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University

3 Institute of Molecular Medicine and Bioengineering, College of Biological Science and Technology, National Yang Ming Chiao Tung University

Owing to the absence of reliable predictive biomarkers and the lack of noticeable symptoms in the early stages, effective diagnosis and treatment of hepatocellular carcinoma (HCC) remain challenging. In the process of cancer development, exosomes released from tumor cells transport functional molecules to neighboring recipient cells, thereby actively participating in the regulation of cancer progression. DDX3, a DEAD-box RNA helicase, plays numerous essential roles in various cellular processes and is consequently implicated as a tumor suppressor in HCC. However, the impact of DDX3 on the secretion and cargo sorting of HCC exosomes remains elusive. Our study revealed that diminished DDX3 expression in HCC cells promoted the release of exosomes and increased the expression of several exosome biogenesis-associated proteins, including exosome markers (e.g., TSG101, Alix, and CD63) and Rab proteins (e.g., Rab5, Rab11, and Rab35). Through double knockdown of DDX3 and these exosome biogenesis-related factors, we confirmed that DDX3 is involved in the regulation of exosome secretion by modulating the expression of these cellular factors in HCC cells. Additionally, exosomes derived from DDX3-knockdown HCC cells enhanced cancer stem cell properties, such as self-renewal capability, migration, and drug resistance, in recipient HCC cells. Through animal experiments, we also discovered that these exosomes significantly promote tumor growth in mice. Furthermore, an increase in the expression of exosome markers TSG101, Alix, and CD63, along with a decrease in tumor-suppressive miR-200b and miR-200c, was found in exosomes derived from DDX3-knockdown HCC cells. These alterations may contribute to the strengthened hepatic cancer stemness observed in recipient cells treated with exosomes from DDX3-knockdown HCC cells. In summary, our findings unveil a new molecular mechanism supporting the tumor-suppressor role of DDX3 in HCC, offering insights that may contribute to developing novel therapeutic strategies against HCC.