RNA

Part:BBa_K3063901

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


eSIBR construct fragment for STAT3

The part encodes artificial microRNA (amiRNA) that silences signal transducer and activator of transcription 3 (STAT3), a member of the STAT protein family for maintaining cancer stemness. [1] For instance, the overactive transcription of STAT3 gene signals cells to grow and divide uncontrollably, and prevent damaged cell to undergo apoptosis[2]. STAT3-targeting amiRNA in the transformed salmonella, will form dsRNA upon binding to stemness STAT3 mRNA in tumour cells. Under the aid of this particular biobrick, RNA silencing and degradation of STAT3 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 STAT3 silencing in cancer stem cells

BBa_K3063901 The BioBrick encodes STAT3 targeting amiRNA. 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 STAT3 knockdown in target cancer cells.

T--Hong_Kong_HKU--STAT3.jpg

Part Therapeutics

Recent findings have demonstrated that STAT3-mediated signaling is implicated in regulating the undifferentiated phenotype of stem cells and suppressing antitumor immunity, while in vitro silencing is capable of inducing G2/M arrest in a variety of cancer cell types. [3] [4] [5] Hence, we postulated that STAT3-targeting amiRNA, carried by salmonella, can effectively silence STAT3 expression in liver stem cells, which in turns minimises the cancer stemness.

References

  1. ↑ Zhang, H. F., & Lai, R. (2014). STAT3 in cancer—friend or foe?. Cancers, 6(3), 1408-1440.
  2. ↑ STAT3 gene - Genetics Home Reference - NIH. (n.d.). Retrieved from https://ghr.nlm.nih.gov/gene/STAT3#conditions.
  3. ↑ Galoczova, M., Coates, P., & Vojtesek, B. (2018). STAT3, stem cells, cancer stem cells and p63. Cellular & molecular biology letters, 23(1), 12.
  4. ↑ Raz, R., Lee, C. K., Cannizzaro, L. A., d’Eustachio, P., & Levy, D. E. (1999). Essential role of STAT3 for embryonic stem cell pluripotency. Proceedings of the National Academy of Sciences, 96(6), 2846-2851.
  5. ↑ Li, J., Liu, Y. Y., Yang, X. F., Shen, D. F., Sun, H. Z., Huang, K. Q., & Zheng, H. C. (2018). Effects and mechanism of STAT3 silencing on the growth and apoptosis of colorectal cancer cells. Oncology letters, 16(5), 5575-5582.
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