Endometrial cancer is a common malignant tumor of the female reproductive system, among which type I endometrial cancer accounts for more than 70%, and its occurrence is related to the stimulation of unopposed estrogen. Endometrial hyperplasia is associated with endometrial cancer, and 1% to 3% of patients with endometrial hyperplasia develop cancer; atypical hyperplasia has a higher risk of cancer than simple or complex hyperplasia, 30% to 40% of patients with dysplasia with adenocarcinoma.

Target genes delivered in vivo in Endometrial Cancer

Figure 1. Targetable pathways for the treatment of endometrial cancer. (Dedes KJ, et al.; 2011)

AEG-1

AEG-1, also known as MTDH gene, is located in the 8q22 region of chromosome, consists of 12 exons and 11 introns, and encodes a protein consisting of 582 amino acids with a molecular weight of 64 kD. AEG-1 gene is low-expressed or absent in normal tissues, highly expressed in the nucleus or cytoplasm of different types of malignant cells, and plays an important role in tissue proliferation, angiogenesis, invasion, and tumor metastasis. AEG-1 gene can promote the transcription of NF-κB downstream genes during tumor invasion by interacting with the p65 subunit of NF-κB; upregulate epithelial-mesenchymal transition (EMT) and metastasis eIF4E mediates the expression of MMP-9 and Twist. In addition, it affects the PI3K/AKT pathway; enhances the expression of HIF1-α and MMP-1 genes, promotes tumor tissue angiogenesis, and provides sufficient nourishment for the growth of tumor tissue. Its expression level in endometrial carcinoma was significantly higher than that in normal endometrial tissue and endometrial atypical hyperplasia tissue, and the main expression sites were cytoplasm and nucleus.

CA125

CA125 gene CA125, also known as MUC16, is located in the chromosome 19p13.2 region, the cDNA is 5 797 bp in length, and the shape is circular, encoding a high molecular glycoprotein, belonging to IgG1, composed of galactose, N-acetylglucosamine and N-acetyl composed of galactosamine chains. The CA125 gene is mainly located in the coelom epithelial cells during embryonic development, and its expression products are mainly located in the bronchial mucosal epithelium, thoracic peritoneum, and fallopian tube epithelium. Serum CA125 concentration may be slightly higher in women during menstruation or in patients with endometriosis; while in patients with endometrial cancer, CA125 is often highly expressed in serum. The study found that the tumor invasion of CA125 and endometrial cancer is related to the angiogenesis of tumor tissue.

SOX2

The SOX2 gene is located in the chromosome 3q26.3-27 region, with a total length of about 2 518 bp, and the structure is a single exon; it consists of a C-terminus containing a transcriptional activation functional region, an HMG-box DNA binding domain and a functional Unidentified N-terminal composition, encoding a protein of 317 amino acids. SOX2 is a transcription factor that regulates cell development, affects cell signal transduction pathways, and plays an important role in transcription, translation, and post-translational processes. SOX2 has stem cell properties and can maintain the pluripotent differentiation and self-renewal capacity of stem cells in the embryonic stage. SOX2 is involved in a variety of proto-oncogenes in tumorigenesis, proliferation and metastasis, and is highly expressed in cervical cancer, ovarian cancer, lung cancer, breast cancer, gastric cancer, colorectal cancer, prostate cancer and glioma. SOX2 is associated with increased cancer aggressiveness, resistance to chemotherapeutics and reduced patient survival, suggesting that SOX2 is also a target for cancer therapy. SOX2 also plays an important role in the occurrence, proliferation and metastasis of endometrial cancer. The study found that knocking down the level of SOX2 in mice with endometrial cancer significantly inhibited tumor growth; SOX2 was silenced in normal endometrial cells and highly expressed in endometrial cancer cells.

Maspin

Maspin gene is located in the chromosome 18g21.3 region, with a full length of 2 584 bp, including a 5' end with 75 non-transcriptional nucleotides and a 3' end with 1 381 nucleotides; it encodes 375 amino acid residues, proteins with a molecular weight of about 42 kD. The binding of maspin to cardiolipin in mitochondria can trigger apoptosis, inhibit EMT by blocking the ITGB1/FAK pathway, regulate VEGF and bFGF, change ECM, and ultimately reduce angiogenesis, thereby inhibiting tumor invasion and metastasis. Maspin is also involved in the malignant biological process of endometrial cancer, and the expression level of Maspin gradually decreases in normal endometrial, atypical endometrial hyperplasia and endometrial cancer.

Estrogen receptor (ER), progesterone receptor (PR) genes

The growth and exfoliation of normal endometrium depends on the regulation of cyclic estrogen and progesterone. The mechanism is that after estrogen and progesterone bind to the corresponding receptors, it activates genes on the endometrium, initiates transcription and synthesizes new proteins, thereby ensuring the physiological functions of membranes. Studies have shown that ER and PR play a key role in the biological process of the occurrence and development of endometrial cancer. The positive expression rate of ER and PR in normal endometrium is 90% to 100%, while the positive expression rate in endometrial cancer is about 50%, which is significantly lower than that in adjacent tissues.

In addition to the above genes, there are interesting endometrial cancer-related genes that need to be explored and studied. Therefore, there is a need for an in vivo transfection system that can precisely target endometrial cancer tissue and be taken up by tumor cells to function in vivo. The 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 endometrial cancer tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the endometrial 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 endometrial 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.

References

1. SU Z Z, et al.; Identification and cloning of human astrocyte genes displaying elevated expression after in-fection with HIV-1 or exposure to HIV-1 envelope glycoprotein by rapid subtraction hybridization, RaSH. Oncogene. 2002, 21(22): 3592-3602.
2. Knific T, et al.; Novel algorithm including CA-125, HE4 and body mass index in the diagnosis of endometrial cancer. Gynecol Oncol. 2017, 147(1):126-132.
3. DANIEL N, et al.; SOX2 in development and cancer biology. Semin Cancer Biol. 2020, 67(Pt1): 74-82.
4. SIMONA G, IOAN J. Subcellular expression of maspin in colorectal cancer:friend or foe. Cancers. 2021,13(3): 366.
5. Dedes KJ, et al.; Emerging therapeutic targets in endometrial cancer. Nat Rev Clin Oncol. 2011, 8(5):261-71.

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