Small cell lung cancer (SCLC) is a type of highly malignant lung cancer. Although it only accounts for 13%-15% of lung cancer, its mortality rate is extremely high. Relevant studies have shown that SCLC is the result of accumulation of changes at multiple molecular levels, and single-target inhibition has limited therapeutic effect on SCLC. Due to the complexity of SCLC and the ambiguity of its pathogenesis, researchers cannot determine the target of targeted therapy, so we need to study the genes related to the occurrence and development of SCLC more deeply.

Target Genes Delivered In Vivo in Small Cell Lung Cancer

Through bioinformatics analysis, it was found that the most critical network central genes among abnormally expressed genes in small cell lung cancer are: TP53, CCL2, FGF2, FOS, FGFR4, PGF.

Figure 1. ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer. (Pozo K, et al.; 2021)

TP53

TP53 is one of the genes most related to human tumors, encoding the production of tumor protein p53. Studies have found that in the activities of normal human cells, TP53 plays a role in maintaining genome stability and regulating cell differentiation by participating in cell regulation and promoting DNA repair and other processes. TP53 was significantly enriched in the process of cell apoptosis and p53, PI3K-Akt and other signaling pathways. The PI3K-Akt signaling pathway composed of PI3K and its downstream molecular protein kinase plays a key role in the occurrence and development of human tumors. TP53 may inhibit the expression of tumor cells and promote apoptosis through this process and metabolic pathways, which plays a key role in the mechanism of SCLC.

CCL2

CCL2 protein is a member of the CC subfamily of chemokines, which can chemoattract monocytes, macrophages, and memory T cells to the site of infection, and plays a role in the occurrence and development of various diseases such as tumors and immune system diseases. It can enhance the invasion ability of tumor cells, promote tumor metastasis, and lead to disease progression.  Study found that the expression of CCL2 was significantly down-regulated in the cells treated with drugs, and it was significantly enriched in the cellular components of the extracellular space and participated in the heparin binding function, which indicated that the down-regulation of CCL2 may be through the regulation of extracellular space Heparin-binding function and other pathways suppress carcinogenesis in SCLC.

FGF2

Fibroblast Growth Factor 2 (FGF2) is a typical class of polypeptides among members of the fibroblast growth factor family, which can promote angiogenesis, wound repair, tissue regeneration and other functions. Studies have found that it can promote the expression of apoptosis inhibitory protein in small cell lung cancer cells through the PKC signaling pathway, thereby inhibiting cell apoptosis.

FOS

FOS protein is a regulator of cell proliferation, differentiation, and the like. The study found that FOS was upregulated in drug-treated cells and downregulated in cancer cells, and was significantly enriched in the cellular components of neuron projections, which may play a role in the regulation of carcinogenesis through this process.

PGF

Placenta growth factor (PGF) is a placental growth factor.  The expression of PGF was significantly down-regulated in cells treated with drugs, and significantly up-regulated in cancer tissues. It was significantly enriched in the process of angiogenesis and organ regeneration. It also participates in molecular functions such as heparin binding and PI3K-Akt signaling pathway, and may play a role in promoting tumor cell growth.

FGFR4

Fibroblast Growth Factor Receptor 4 (FGFR4) is a transmembrane receptor tyrosine kinase and a member of the fibroblast growth factor receptors.  FGF2 exerts biological effects mainly by binding with high affinity to FGFRs on the cell surface. Studies have found that FGF2 and FGFR4 are closely related to the invasion and metastasis of SCLC.  Studies have shown that the expression of FGF2 is significantly down-regulated in drug-treated cells and significantly up-regulated in cancer tissues, while the expression of FGFR4 is significantly up-regulated in drug-treated cells and down-regulated in cancer tissues.  These two genes jointly play the molecular function of heparin binding and are enriched in the PI3K-Akt signaling pathway with PGF and TP53, indicating that the gene expression results may regulate the development of SCLC by affecting heparin binding and PI3K-Akt signaling pathway, and prevent FGF2 from interacting with it.  The binding of receptors inhibits the proliferation of cancer cells.

In addition to the above genes, there are interesting small cell lung 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 small cell lung 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 small cell lung cancer tissues and cells, and is toxic to the body;
• The in vivo transfection system used cannot penetrate the small cell lung 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 small cell lung 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. van Meerbeeck JP, et al.; Small-cell lung cancer. Lancet. 2011, 378(9804):1741-55.
2. Gong L, et al.; Integrated Bioinformatics Analysis for Identificating the Therapeutic Targets of Aspirin in Small Cell Lung Cancer. J Biomed Inform. 2018, 88:20-28.
3. Ganti AKP, et al.; Small Cell Lung Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021,19(12):1441-1464.
4. Pozo K, et al.; ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer. iScience. 2021, 24(9):102953.

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