Control of TGFA Expression is Expected to Reduce Cervical Cancer Incidence

It is a protein that is generated by macrophages, brain cells and epidermal cells called transforming growth factor- (TGFA). TGFA is a ligand for the epidermal growth factor receptor and a member of the polypeptide growth factor family, epidermal growth factor (EGF), and is therefore part of this family. This small polypeptide, transforming growth factor, solves the epithelialisation puzzle and turns cells of every sort of type into another kind. TGFA engages the epidermal growth factor receptor at its high-affinity site and, more specifically, stimulates the epidermal growth factor receptor's own tyrosine kinase, leading to a chain reaction and consequently, a biological switch. The interaction of TGFA with the epidermal growth factor receptor activates the RAS/Raf/MAPK and PI3K/AKT pathways that lead to cell proliferation and invasion, apoptotic inhibition and angiogenesis. In some human cancers, including cervical cancer, TGFA is highly present. So it can be utilized as a biomarker to forecast patients' prognosis.

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TGFA-related Diseases

TGFA is a generalized cell growth factor involved in cell proliferation, differentiation and survival. TGFA has many physiological and pathological roles. The diseases of it are basically:

Expression of TGFA in Different Tissues

The Harm of Cervical Cancer

The most common cancers that kill 20-39 years old women are cervical squamous cell carcinoma and cervical adenocarcinoma (CESC), 2022 Cancer Statistics shows. It is a cancerous growth in the female organ and normally develops in the cells of the cervix. It's a cervix cancer, it multiplies cells. HPV of many different varieties is the most common form of cervical cancer. The HPV is a sex-borne virus. The human immune system will usually keep the virus from getting into us when we contract HPV. Women are also prevented from developing cervical cancer with preventive measures such as annual cervical cancer screening (Pap smear test) and HPV vaccine. And therefore, novel biomarkers are needed to estimate the patient outcomes and pinpoint target therapy.

TGFA and Cervical Cancer

TGF is abundant in tissues and cells of cervical cancer. TGFA knockdown can prevent cervical cancer cells from growing, spreading and invading. Furthermore, CESC cell lines expressed significantly less of the IL family and MMP family proteins after TGFA knockout. TGF-EGFR expression is increased, and tumors can grow by way of autocrine growth factor stimulation. TGFA therefore also plays a role in the pathogenesis and progression of cervical cancer, and so TGFA could be an interesting target for cervical cancer therapy.

Figuring out how TGFA works and what disease it contributes to will lead to new treatment approaches and biomarkers, but much remains to be done to define its function and potential for clinical application.

Fig. 1 Functional validation of TGFA in CESC cell lines (Ma, XX, et al. 2024).

Test of TGFA-related Differentially Expressed Genes

TGFA has direct associations with cell proliferation, differentiation and survival. TGFA might be involved in tumours, growth and development and some diseases. To investigate TGFA differentially expressed genes, differentially expressed genes that were screenable were functionally annotated and pathway enrichment measured. Most commonly implemented methods are GO and KEGG analysis. A GO and KEGG analysis identified TGFA as correlated with keratin and keratinocyte differentiation. So TGFA could control tumor cell growth and migration in this way.

Functional Validation of TGFA

TGFA is used in several biological processes across a variety of cells, including proliferation, differentiation and migration. To suppress TGFA expression, CESC incidence, metastasis and invasiveness can be diminished and anti-tumor immunity boosted. When it comes to functional validation of TGFA in CESC (cervical squamous cell carcinoma) cell lines, the following are normally involved:

Basic Expression Analysis

Expression levels of TGFA in CESC cell lines are assessed by RT-qPCR or Western blot and the differences between normal cells or other cancer cells and CESC cell lines are compared.

Cell Proliferation Experiment

MTT, CCK-8 or BrdU suspect experiments are performed to investigate the role of TGFA overexpression or knockout in CESC cell proliferation to try to figure out what the regulatory role of TGFA plays in cell growth.

Cell Migration and Invasion Assay

The ability of CESC cells to migrate and invade is tested by scratch assay or metastasis assay, TGFA's contribution.

Signaling Pathway Analysis

The activation of TGFA-like signaling pathways (ERK, PI3K/Akt, etc.) were uncovered by Western blot and other techniques to learn more about the TGFA action on CESC cells.

Function-related Biological Experiments

Apoptosis analysis (Annexin V/PI staining, etc) is available to quantify the effect of TGFA on CESC cell survival and apoptosis.

Conclusion

Tissues containing TGFA are more abundant than cells of normal origin, but not in precancerous tissue; this means that TGFA might be involved in transforming cervical cancer. TGFA is expressed high in CESC and TGFA is associated with CESC occurrence and progression. Deficiency of TGFA expression will decrease CESC incidence, metastasis and invasion and promote anti-tumor immunity. TGFA, then, can be a standalone risk factor for CESC and a realistic molecular marker for CESC diagnosis, treatment and prognosis prediction, allowing physicians to design more individualised treatment strategies for patients.

Reference

1. Ma, XX, et al. TGFA expression is associated with poor prognosis and promotes the development of cervical cancer. Journal of Cellular and Molecular Medicine. 2024, 28(3): e18086.