GATA3: Analyzing a transcription factor involved in ovarian cancer

Avani Dave, Jai Hind College

Ovarian cancer (OC) is among the most devastating gynaecological cancers, with high incidence and mortality rates across the world, putting women’s health and quality of life at risk. Although radical surgery and chemotherapy are two essential treatments for treating OC, they do not appear to diminish the high recurrence rate of the disease or enhance the patient’s prognosis. Patients with OC have a 5-year survival rate of less than 35% worldwide. As a result, it is critical to get a better knowledge of the pathophysiology of OC to discover and develop more effective therapeutic targets for the disease’s therapy.

Non-structure maintenance of chromosome condensin I complex subunit H (NCAPH) is a subunit of the condensin I complex, which belongs to the kleisins, a newly identified superfamily of proteins. There is strong evidence that aberrant NCAPH expression has a role in the development of a variety of human cancers. NCAPH is increased in prostate cancer, for example, and silencing NCAPH inhibits cell growth and metastasis. NCAPH seems to act as an oncogene in endometrial cancer and breast cancer, and its high expression is associated with a bad prognosis.

GATA binding protein 3 (GATA3) is a highly conserved zinc-finger transcription factor that is involved in a variety of cellular activities like proliferation, invasion, DNA repair, and senescence. GATA3 has been linked to a variety of human malignancies, including liver cancer, breast cancer, and endometrial carcinomas. GATA3 functions as an oncogenic protein in high-grade serous ovarian cancer and high expression are linked to a poor prognosis in patients. 

A recent study conducted by Yingying Qi aimed to see if GATA3 can trigger NCAPH expression through transcription to help with OC development. This research looked at the effects of NCAPH on OSCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as the regulatory effects and possible mechanisms of OC development. 

Results: 

It was initially demonstrated that NCAPH is elevated in serous ovarian cancer, suggesting that it may be implicated in the disease’s carcinogenesis and carboplatin resistance and that it may be used as a prognostic indicator for patients with carboplatin resistance. The role of NCAPH in the development of OC, on the other hand, is yet unknown.

In OC tissues and cell lines, NCAPH and GATA3 expression were considerably increased. Proliferation, migration, invasion, and EMT of OC cells were all reduced by NCAPH loss-of-function. Additionally, NCAPH knockdown reduced the expression of p-PI3K, PDK1, and p-AKT. GATA3 also binds to the NCAPH promoter, which has been verified. NCAPH silencing inhibited OC cell proliferation, migration, invasion, EMT, and protein production in the PI3K/PDK1/AKT pathway, while GATA3 overexpression relieved this impact.

The future prospects of the study:

To summarize the findings, this is the first work to show that silencing NCAPH reduces OC cell proliferation, migration, invasion, and EMT. By binding to the NCAPH promoter, GATA3 has been shown to directly influence NCAPH transcription. GATA3-induced NCAPH activation affects the PI3K/PDK1/AKT signalling pathway, which controls the development of OC mechanically. These findings illuminate the mechanism of GATA3/NCAPH in OC and provide potential therapeutic options.

The current study’s limitations include a lack of data on the effects of NCAPH and GATA3 on the development and metastasis of OC in vivo, as well as the use of agonists or inhibitors of the PI3K/PDK1/AKT signalling pathway, which will be studied in future trials to further support the findings. Although the findings pave the way for a novel approach to OC therapy, a more comprehensive analysis of the underlying mechanism is desired.

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Reference: Qi, Y., Mo, K., & Zhang, T. (2021). A transcription factor that promotes proliferation, migration, invasion, and epithelial–mesenchymal transition of ovarian cancer cells and its possible mechanisms. Biomedical Engineering Online, 20(1), 83. https://doi.org/10.1186/s12938-021-00919-y

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Author’s Info: Avani Dave is currently in the final year of her bachelor’s degree, majoring in Life Sciences. Holding a good academic and extra-curricular record, she is on a constant journey of acquiring exposure in her field of interest while simultaneously not limiting herself to just that. Avani likes studying Diseases and Syndromes and everything under this umbrella! That being said, she is adept at working across departments and promises to deliver.