講師資料
Talks：
Core clock gene PER2 inhibits epithelial-mesenchymal transition and prevents cisplatin resistance in Epi-A ovarian cancer
核心時鐘基因 PER2 抑制 Epi-A 卵巢癌上皮間質轉化與Cisplatin抗藥性
Name：
黃雯華（Wendy W. Hwang-Verslues）
Position：
Associate Research Fellow (equivalent to Associate Professor)
Affiliation：
Genomics Research Center, Academia Sinica
Email：
Photo：
Research Interests：
Cancer Biology, Circadian Biology, Molecular Biology, Molecular Toxicology
Selected Publications：
1. Wang C.-K., Chen T.-J., Tan G.Y.T., Chang F.-P., Sridharan S., Yu C.-H.A., Chang Y.-H., Chen Y.-J., Cheng L.-T., Hwang-Verslues W.W.* [2023] MEX3A mediates p53 degradation to suppress ferroptosis and facilitate ovarian cancer tumorigenesis. Cancer Research, 83(2):251-263 doi: 10.1158/0008-5472.CAN-22-1159, PMID: 3635437420.
2. Cheng L.-T., Tan G.Y.T, Chang F.-P., Wang C.-K., Chou Y.-C., Hsu P.-H., Hwang-Verslues W.W.* [2023] Core clock gene BMAL1 and RNA-binding protein MEX3A collaboratively regulate Lgr5 expression in intestinal crypt cells. Scientific Reports, 13, 17597, PMID: 37845346.
3. Chang P.-H., Chen M.-C., Tsai Y.-P., Tan G.Y.T., Hsu P.-H., Jeng Y.-M., Tsai T.-F., Yang M.-H., Hwang-Verslues W.W.* [2021] Interplay between Desmoglein2 and hypoxia controls metastasis in breast cancer. Proceedings of National Academy of Sciences, U.S.A. 118 (3) e2014408118; https://doi.org/10.1073/pnas.2014408118, PMID: 33431674
4. Chen L.-C., Hsieh Y.-L., Tan G.Y.T., Kuo T.-Y., Chou Y.-C., Hsu P.H., Hwang-Verslues W.W.* [2021] Differential Effects of SUMO1 and SUMO2 on Circadian Protein PER2 Stability and Function. Scientific Reports, 13;11(1):14431. doi: 10.1038/s41598-021-93933-y, PMID: 342573720
5. Yu C.-W., Cheng K.-C., Chen L.-C., Lin M.-X., Chang Y.-C., Hwang-Verslues W.W.* [2018] Pro-inflammatory cytokines IL-6 and CCL2 suppress expression of circadian gene Period2 in mammary epithelial cells. Biochimica et Biophysica Acta Gene Regulatory Mechanisms 1861(11):1007-1017, PMID: 30343691
6. Wu H.-H¥, Hwang-Verslues W.W. ¥, Lee W.-H., Huang C.-K., Wei P.-C., Chen C.-L., Shew J.-Y., Lee E. Y.-H. P., Jeng Y.-M., Tien Y.-W., Ma C., Lee W.-H.* [2015] Targeting IL-17B/RB signaling with an anti-IL17RB antibody blocks pancreatic cancer metastasis by silencing multiple chemokines. Journal of Experimental Medicine 212(3):333-49. (¥ equal contribution).
7. Hwang-Verslues W.W., Chang P.-H., Jeng Y.-M., Kou W.-H., Chang Y.-C., Chiang P.-H., Hsieh T.-H., Su F.-Y., Lin L.-C., Abbondante S., Yang C.-Y., Hsu H.-M., Yu J.-C., Chang K.-J., Shew J.-Y., Lee E. Y.-H. P., Lee W.-H.* [2013] Loss of corepressor PER2 under hypoxia upregulates OCT1-mediated EMT gene expression and enhances tumor malignancy. Proceedings of National Academy of Sciences, U.S.A. 110(30):12331-12336.
Abstract：
Ovarian cancer (OC) is highly heterogenous, metastatic and chemoresistant. These malignant phenotypes are strongly associated with epithelial-mesenchymal transition (EMT). Five distinct gene-expression based molecular subtypes (GEMS) of OC have been characterized and correlated with different EMT levels and patient survival. However, the regulatory mechanism underlying GEMS-specific EMT and malignancy remain unclear.
We found that core clock gene PER2 expression was significantly downregulated in OC compared to normal ovarian tissues. Among the GEMS, PER2 expression was high in the Epithelial-A (Epi-A) subtype and Epi-A OC patients with higher PER2 had better overall survival. Notably, PER2 expression was required to maintain the epithelial phenotype of Epi-A OC cells. Depletion of PER2 increased reactive oxygen species (ROS), elevated Heme oxygenase-1 (HO-1) to drive EMT, and consequently enhanced migration and invasion ability of the Epi-A OC cells. PER2 depletion also increased cisplatin resistance in Epi-A OC cells. Conversely, inhibition of HO-1 in PER2-depleted Epi-A OC cells impeded invasion and migration, as well as sensitized PER2-depleted Epi-A OC cells to cisplatin. Our results identified PER2 as a critical factor preventing Epi-A OC EMT and malignancy. These observations also indicated that preventing PER2 downregulation and targeting HO-1 can be potential strategies for treating Epi-A OC progression.
2024年會：
10/13 11:00 Core clock gene PER2 inhibits epithelial-mesenchymal transition and prevents cisplatin resistance in Epi-A ovarian cancer
核心時鐘基因 PER2 抑制 Epi-A 卵巢癌上皮間質轉化與Cisplatin抗藥性 [會議室4]