Colorectal cancer is one of the major human malignancies, and its morbidity and mortality ranks third and fourth, respectively. Each year, 1.2 million new cases are diagnosed and more than 600,000 patients die from colorectal cancer. Colorectal cancer incidence is low in the under-50s, but increases with age.

Figure 1. The activation and regulation mechanisms of oncogenic transcription factors in CRC. (Xu H, et al.; 2021)

Colorectal cancer is a disease that originates in the colon or rectal epithelial cells of the gastrointestinal tract and is most commonly caused by mutations in the Wnt signaling pathway that increase signaling activity. Mutations can be inherited or acquired, and are most likely to occur in intestinal crypt stem cells. The most commonly mutated gene in all colorectal cancers is the APC gene, which produces the APC protein. APC protein prevents accumulation of β-catenin protein. In the absence of APC, β-catenin accumulates to high levels and translocates (moves) into the nucleus, binds to DNA, and activates transcription of proto-oncogenes. These genes are often important for stem cell renewal and differentiation, but when expressed at inappropriately high levels, they can lead to cancer.

In addition to defects in the Wnt signaling pathway, other mutations must occur in cells to become cancerous. The p53 protein produced by the TP53 gene normally monitors cell division and induces programmed cell death when they are defective in the Wnt pathway. Ultimately, the cell line acquired a mutation in the TP53 gene and transformed the tissue from a benign epithelial tumor to an aggressive epithelial cell carcinoma. Sometimes the gene encoding p53 is not mutated, but another protective protein called BAX is mutated.

Other proteins that cause programmed cell death that are commonly inactivated in colorectal cancer are TGF-β and DCC. TGF-β has inactivating mutations in at least half of colorectal cancers. Sometimes TGF-β is not inactivated, but a downstream protein called SMAD is inactivated.

About 70% of human genes are expressed in colorectal cancer, and only more than 1% of genes are increased in colorectal cancer compared to other forms of cancer. Some genes are oncogenes: they are overexpressed in colorectal cancer. For example, genes encoding the proteins KRAS, RAF and PI3K normally stimulate cell division in response to growth factors, but they can acquire mutations that lead to hyperactivation of cell proliferation.

Comprehensive genome-scale analysis revealed that colorectal cancer can be divided into hypermutated and non-hypermutated tumor types. In addition to oncogenic and inactivating mutations in the above-mentioned genes, non-hypermutated samples also contained mutated CTNNB1, FAM123B, SOX9, ATM, and ARID1A. Progressing through a distinct set of genetic events, hypermutated tumors display mutated forms of ACVR2A, TGFBR2, MSH3, MSH6, SLC9A9, TCF7L2, and BRAF. A common theme of these genes in both tumor types is their involvement in Wnt and TGF-β signaling pathway, which leads to increased activity of MYC. MYC is a central player in the initiation and progression of colorectal cancer.

Therefore, for further therapeutic exploration of colorectal cancer, precise molecular functional studies are essential. However, the use of genetic engineering techniques such as RNA interference or Cas9 system to conduct functional studies at the gene level In Vivo requires an In Vivo transfection system that can precisely target colorectal cancer tissues and be absorbed by tumor cells to play a role in the cells. This system can help researchers overcome various challenges encountered during In Vivo transfection:

• Relevant molecular function studies can only be carried out in vitro, lacking important In Vivo data
• Using in vitro transfection system for In Vivo transfection, the transfection efficiency is very low;
• The In Vivo transfection system used is not specific to colorectal cancer tissues and cells, and is toxic to the body;
• The In Vivo transfection system used cannot penetrate the colorectal cancer tissue into the tumor tissue;
• The nucleic acid load of the In Vivo transfection system is low, and it is difficult to achieve the expected effect;
• Etc…

Our Advantage:

• We can provide an In Vivo transfection system for colorectal cancer tissues and cells to achieve efficient transfection
• Our system can target multiple targets at the same time, improving targeting accuracy
• The In Vivo transfection system has low toxicity to the body and is safe to use
• In Vivo transfection system vectors can protect nucleic acids from degradation during In Vivo delivery
• Persistent knockout effect in experimental animals after a single injection
• The system load is high, and the transfection needs of different doses can be completed
• Professional design and service team to provide you with reliable service and technical support
• Timely feedback of technical reports

CD BioSciences specializes in developing transfection systems and customizing transfection reagents for gene transfection using our core technologies. With our high-quality products and services, your transfection results can be greatly improved. If you can't find a perfect In Vivo transfection system, you can contact us. We can provide one-to-one personal customization service.

Reference

1. Xu H, et al.; Transcription factors in colorectal cancer: molecular mechanism and therapeutic implications. Oncogene. 2021, 40(9):1555-1569.

* For research use only. Not for use in clinical diagnosis or treatment of humans or animals.