RNA

Part:BBa_K3063903

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

eSIBR construct fragment for SOX9

The part encodes artificial microRNA (amiRNA) that silences SOX9, a gene promoting cancer metastasis and driving cancer cell growth. [1] SOX9-targeting amiRNA in the transformed salmonella, will form dsRNA upon binding to stemness SOX9 mRNA in tumour cells. Under the aid of this particular biobrick, RNA silencing and degradation of SOX9 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 SOX9 silencing in cancer stem cells

BBa_K3063903 The part for SOX9 silencing in cancer stem cells. With the help of 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, achieving SOX9 knockdown in target cancer cells.

T--Hong_Kong_HKU--SOX9.jpg

Part Therapeutics

Sox9 has long been known to overexpress in tumor, in particular, cancer stem cells. It maintains self-renewal capacity of CSCs through constitutive activation of Notch signalling pathway [2] Metastatic cells show further elevation of Sox9 than non-metastatic ones, indicating the role of the gene in cancer progression, possibly via Wnt/β-catenin signaling. [3]

References

  1. ↑ Carrasco-Garcia, E., Lopez, L., Aldaz, P., Arevalo, S., Aldaregia, J., Egaña, L., ... & Matheu, A. (2016). SOX9-regulated cell plasticity in colorectal metastasis is attenuated by rapamycin. Scientific reports, 6, 32350.
  2. ↑ Liu, C., Liu, L., Chen, X., Cheng, J., Zhang, H., Shen, J., ... & Qian, C. (2016). Sox9 regulates self‐renewal and tumorigenicity by promoting symmetrical cell division of cancer stem cells in hepatocellular carcinoma. Hepatology, 64(1), 117-129.
  3. ↑ Aguilar-Medina, M., Avendaño-Félix, M., Lizárraga-Verdugo, E., Bermúdez, M., Romero-Quintana, J. G., Ramos-Payan, R., ... & López-Camarillo, C. (2019). SOX9 Stem-Cell Factor: Clinical and Functional Relevance in Cancer. Journal of oncology, 2019.
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