Team:CKWA-China/Description
Description
Description
1. A major problem in cancer.
Recurrence of cancer after treatment is a major problem facing humans today, and cancer recurrence is a great threat for cancer patients. Among them, overexpression of c-myc protein is closely related to this process, and patients with overactivation of c-myc gene in cancer cells tend to have poor prognosis.
1.1 What are myc genes?
myc genes have been shown to be a class of regulatory genes that are transcription factors that can encode myc-like proteins to become transcription factors transcription factors. they are essential for cell growth, metabolism and tissue development.
1.2 Impact of myc in cancer
They are essential for cell growth, metabolism and tissue development. Also, MYC is an important group of oncogenes. c-MYC is aberrantly expressed in about 30-50% of human malignancies and plays an extremely important role in affecting cell growth, proliferation, differentiation, apoptosis, as well as cell metabolism and malignant transformation. aberrantly high expression of c-MYC is associated with poor prognosis in many human cancers.
1.3 C-myc genes
The Myc family consists of three related human genes: - c-myc (MYC), the first gene to be discovered in this family - l-myc (MYCL) - n-myc (MYCN)
2. New discoveries.
Scientists have recently discovered that a Lon protease from bacteria can effectively degrade c-myc protein, and this may be one of the reasons why bladder cancer patients with urinary tract infection with this bacteria have a better prognosis instead. Thus, Lon protein is expected to be a new macromolecular drug in the fight against cancer in humans.
2.1 Discovery of c-myc protein inhibition
MYC is important for the growth and development of the kidney. It has been shown that severe kidney infections impair kidney growth in childhood and that bladder cancer in patients with urinary tract infections instead has a better prognosis. Inference: MYC levels in the kidney may be disturbed by bacterial infections.
2.2 Bacterial proteases deplete c-MYC and increase survival in mouse models of bladder and colon cancer
Uropathogenic Escherichia coli (UPEC) can degrade c-MYC protein and attenuate MYC gene expression in human cells and animal tissues. Also, c-MYC protein can be degraded by cell-free Uropathogenic Escherichia coli (UPEC) lysates, as well as rapidly by purified Lon protease.
2.3 Literature conclusions
Lon protease from uropathogenic Escherichia coli (UPEC) is able to degrade c-MYC protein and attenuate MYC gene expression in human cells and animal tissues. Experiments in mouse models have shown that Lon protease delivered either intravesically or orally can delay tumor progression and improve survival in both MYC-dependent bladder and colon cancer models.
3. Our solution
We try to express Lon protease in various systems and test the yield of Lon protease in different environments. After achieving stable laboratory production, we will conduct in vitro cellular experiments to verify the inhibition ability of Lon protease on c-myc, and then we will try to optimize Lon protease from protein structure, find its effective gene fragment, adopt mRNA delivery system, and try to use it The next step will be to try to optimize Lon protease from protein structure, find its effective gene fragment, adopt mRNA delivery system, and try to use it as RNA targeting drug for drug optimization.
Ref
Butler, D.S.C., Cafaro, C., Putze, J. et al. A bacterial protease depletes c-MYC and increases survival in mouse models of bladder and colon cancer. Nat Biotechnol 39, 754–764 (2021). https://doi.org/10.1038/s41587-020-00805-3