Difference between revisions of "Part:BBa K4469005"

Revision as of 15:18, 29 September 2022

alpha-fetoprotein (AFP) promoter

AFP is a glycoprotein produced by the visceral endoderm of the yolk sac during the embryonic period, and under normal physiology, it should remain at low levels throughout the lifespan. However, the re-expression of AFP in patients with hepatocellular carcinoma (HCC) has been observed in 50%-70% of HCC patients. Currently, AFP 400 ng/mL is used as a diagnostic threshold for liver cancer (Bialecki & di Bisceglie, 2005). Among patients of TNM III/IV, over half have an AFP level of 21-400 ng/mL or more (Galle et al., 2019). At the early stage of hepatocarcinogenesis, the AFP gene is reactivated in liver cells. Cytoplasmic AFP promotes malignant liver cells proliferation via induction of Src and c-myc expression. Later, metastasis of liver cancer is further promoted by stimulating the expression of metastasis-related genes (e.g., K19 and EpCAM) (Lu et al., 2016).

AFP promoter has been widely used in gene therapy for HCC. An AFP-miRNA lentiviral vector was efficient in transducing 3 HCC cell lines (HCCLM3, Huh7, Hep3B), with up to 20-fold higher expression in HCC than normal liver cell lines (Peng et al., 2013). Hepatoma (HepG2) cells show 6-fold higher transgene expression than normal liver cells (Hepa) following AFP-contianing construct transfection (Willhauck et al., 2008). Although AFP promoter has high activity and specificity in liver cancers, it is usually used in combination with enhancers due to its relative weakness as compared to universal promoters in driving gene expression.

‘’’Reference’’’

Galle, P. R., Foerster, F., Kudo, M., Chan, S. L., Llovet, J. M., Qin, S., Schelman, W. R., Chintharlapalli, S., Abada, P. B., Sherman, M., & Zhu, A. X. (2019). Biology and significance of alpha-fetoprotein in hepatocellular carcinoma. Liver international : official journal of the International Association for the Study of the Liver, 39(12), 2214–2229. https://doi.org/10.1111/liv.14223

Hu, X., Chen, R., Wei, Q., & Xu, X. (2022). The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We? International Journal of Biological Sciences, 18(2), 536–551. https://doi.org/10.7150/ijbs.64537

Lu, Y., Zhu, M., Li, W., Lin, B., Dong, X., Chen, Y., Xie, X., Guo, J., & Li, M. (2016). Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells. Journal of Cellular and Molecular Medicine, 20(3), 549–558. https://doi.org/10.1111/jcmm.12745

Peng, Y.-F., Shi, Y.-H., Ding, Z.-B., Zhou, J., Qiu, S.-J., Hui, B., Gu, C.-Y., Yang, H., Liu, W.-R., & Fan, J. (2013). Alpha-fetoprotein promoter-driven CRE/LoxP-switched RNA interference for hepatocellular carcinoma tissue-specific target therapy. PLoS ONE, 8(2). https://doi.org/10.1371/journal.pone.0053072

Willhauck, M., Sharif Samani, B., Klutz, K. et al. α-Fetoprotein promoter-targeted sodium iodide symporter gene therapy of hepatocellular carcinoma. Gene Ther 15, 214–223 (2008). https://doi-org.easyaccess1.lib.cuhk.edu.hk/10.1038/sj.gt.330305

Sequence and Features