Thyroid cancer (TC) is the most common endocrine malignancy. In recent years, its incidence has gradually increased, and it has attracted much attention from the public and medical staff. Studies have shown that thyroid cancer is divided into differentiated thyroid cancer (DTC), medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC), and DTC is further divided into papillary thyroid cancer. Papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). DTC is the most common clinically, accounting for about 90%, and the prognosis is generally good. However, some patients with thyroid cancer have local organ invasion, neck lymphatic metastasis or distant organ metastasis in the early stage, which seriously affects the quality of life and survival of patients. Poorly differentiated thyroid cancer (PDTC) is generally considered to be derived from DTC, and its biological behavior is between DTC and ATC. Papillary thyroid microcarcinoma (PTMC) generally has a good prognosis, but 15% to 20% still have recurrence, cervical lymph node metastasis or distant organ metastasis, and even life-threatening. Therefore, it is necessary to conduct in-depth molecular function research on its related genes to facilitate the development of clinical drugs in the later stage.

Target Genes Delivered In Vivo in Thyroid Cancer

Through years of continuous development and research of molecular biology techniques, RAS, RET/PTC, TP53, TERT, PTEN, b-catenin, PAX8/PPAR, BRAF, PIK3CA, AKT1, STRN/ALK, ETV6/NRTK3, and EIF1AX and other mutant genes have been discovered in thyroid cancer

Figure 1. Influencers on Thyroid Cancer Onset: Molecular Genetic Basis. (Luzón-Toro B, et al.; 2019)

BRAF

BRAF is involved in the signaling of cell division and the process of cell growth in cells. Mutated (altered) forms of the BRAF gene and protein are found in many types of cancer. These changes increase the growth and spread of cancer cells. Studies have found that the mutation rate of BRAF in PTC can reach 80%. This indicates that BRAF may be a potential target in the development of PTC therapeutic drugs.

RAS

Ras proteins are members of a large family of small GTP-binding proteins.  It affects cell growth, differentiation, cytoskeleton, protein transport and secretion, etc., and its activity is regulated by binding to GTP or GDP. Existing studies have shown that it is related to tumor formation, proliferation, migration, spread and angiogenesis. The mutation rate in DTC is second only to BRAF, 40%~50% in FTC, 10%~20% in PTC, and the mutation rate in follicular variant papillary thyroid carcinoma (FVPTC) The highest mutation rate is 20% to 40% in non-invasive follicular thyroid neoplasm with papillary like nuclear features (NIFTP). Therefore, it can be used as one of the targets of drug research.

RET/PTC

RET is a proto-oncogene. It encodes a plasma membrane-bound RET tyrosine kinase receptor for the ligand of the glial-derived neurotrophic factor family (GFL).  RET protein is expressed in thyroid parafollicular cells or C cells.  RET/PTC-associated oncogenicity occurs through chromosomal rearrangements, which occur when the C-terminal kinase domain of RET is linked to the promoter and N-terminal domain of an unrelated gene. This rearrangement puts RET under the transcriptional control of its fusion partner gene promoter and allows the chimeric protein of the receptor to be aberrantly expressed in epithelial follicular thyroid cells. Fusion of the RET receptor stimulates the RAS-RAF-MAPK signaling cascade. As a result of the rearrangement, the MAPK pathway becomes unrestricted and chronically activated. Studies have found that the incidence of RET/PTC rearrangement in sporadic PTC is 15%-20%, and it is more common in ionizing radiation and children's PTC. RET/PTC1 rearrangement is the most common, accounting for 60%-80%.

TERT

TERT promoter mutations upregulate TERT mRNA and protein expression and telomere length. The incidence of TERT mutation in DTC is 10%~15%, in PDTC and ATC 40%~45%, but it is rare in benign nodules. Studies have found that TERT promoter mutations play an important role in the dedifferentiation and metastasis of thyroid cancer cells, especially when they coexist with BRAF mutations, the risk of PTC invasion and recurrence increases significantly.

TP53

TP53 encodes a P53 protein that monitors cell cycle DNA damage, regulates cell proliferation, maintains normal cell growth, and inhibits malignant cell proliferation.  TP53 gene mutations are mostly found in exons 5-9, and are common in FVPTC with strong aggressiveness, and more frequent in PDTC and ATC.

In addition to the above genes, there are interesting thyroid 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 thyroid 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 thyroid cancer tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the thyroid 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 thyroid 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. Xing M, et al.; Progress in molecular based management of differentiated thyroid cancer. Lancet. 2013, 381(9871): 1058-1069.
2. Mayson SE, Haugen BR. Molecular diagnostic evaluation of thyroid nodules. Endocrinol Metab Clin North Am. 2019, 48(1): 85-97.
3. Liu R, Xing M. TERT promoter mutations in thyroid cancer. Endocr Relat Cancer. 2016, 23: R143-R155.
4. Cancer Genome Atlas Research Network. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014, 159(3): 676-690.
5. Luzón-Toro B, et al.; Influencers on Thyroid Cancer Onset: Molecular Genetic Basis. Genes (Basel). 2019, 10(11):913.

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