RNA

Part:BBa_K3063902

Designed by: Ng Tsz Chun   Group: iGEM19_Hong_Kong_HKU   (2019-10-15)


eSIBR construct fragment for SOX4

The part encodes artificial microRNA (amiRNA) that silences SOX4, a gene conferring cancer stem cell (CSC) properties. [1] SOX4-targeting amiRNA in the transformed salmonella, will form dsRNA upon binding to stemness SOX4 mRNA in tumour cells. Under the aid of this particular biobrick, RNA silencing and degradation of SOX4 mRNA in liver cancer stem cells can be achieved simultaneously.

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    INCOMPATIBLE WITH RFC[21]
    Illegal XhoI site found at 156
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]


Introduction

Biology

Part structure

The part for SOX4 silencing in cancer stem cells

BBa_K3063902 The BioBrick encodes SOX4 targeting amiRNA. With the help of enhanced enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) vector, pri-miRNA hairpin as shown below is transcribed and later processed into mature miRNA in Salmonella Typhimurium that achieve SOX4 knockdown in target cancer cells.

T--Hong_Kong_HKU--SOX4.jpg

Part Therapeutics

Evidence has been accumulating that SOX4, whose expression initiated by STAT3, orchestrates epithelIal-to-mesenchymal transition (EMT) through upregulating a series of EMT-inducing transcription factors, which then enhances cellular growth as well as transformation. [2] For instance, SOX4 is associated with cell survival in tumour population growth, as well as the metastatic properties of the in vitro [3]. SOX4 knockdown can effectively reduce the activation of transforming growth factor-beta (TGF-β) signalling, attenuating the invasion of cancer cells. [4]

References

  1. ↑ Qi, M., Hu, J., Cui, Y., Jiao, M., Feng, T., Li, X., ... & Zhang, H. (2019). CUL4B promotes prostate cancer progression by forming positive feedback loop with SOX4. Oncogenesis, 8(3), 23.
  2. ↑ Lourenço, A. R., & Coffer, P. J. (2017). SOX4: joining the master regulators of epithelial-to-mesenchymal transition?. Trends in cancer, 3(8), 571-582.
  3. ↑ Grimm, D., Bauer, J., Wise, P., Krüger, M., Simonsen, U., Wehland, M., … Corydon, T. J. (2019). The role of SOX family members in solid tumours and metastasis. Seminars in Cancer Biology. doi: 10.1016/j.semcancer.2019.03.004
  4. ↑ Foronda, M., Martínez, P., Schoeftner, S., Gómez-López, G., Schneider, R., Flores, J. M., ... & Blasco, M. A. (2014). Sox4 links tumor suppression to accelerated aging in mice by modulating stem cell activation. Cell reports, 8(2), 487-500.
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