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LncRNA TP53TG1 plays an anti-oncogenic role in cervical cancer by synthetically regulating transcriptome profile in HeLa cells

ABSTRACT: Long non-coding RNAs (lncRNAs) have been extensively studied as key regulators of cancer development in various cancers. TP53TG1 is a newly identified lncRNA in recent years, and several studies have shown that TP53TG1 may play oncogenic or anti-oncogenic roles in different cancers. Pan-cancer analysis showed that high TP53TG1 expression was significantly associated with better prognosis. Nevertheless, the role of TP53TG1 in the development of cervical cancer is unclear. In our study, we constructed a TP53TG1 overexpression model in HeLa cell line. We found that TP53TG1 overexpression significantly inhibited cell proliferation and induced apoptosis, and TP53TG1 may be a novel anti-oncogenic factor in cervical cancer. Mechanistically, overexpression of TP53TG1 could activate type I interferon signaling pathways and inhibits the expression of genes involved in DNA damage responses. Meanwhile, TP53TG1 could regulate the expression of a large number of RNA binding protein genes thereby potentially affecting the alternative splicing of genes involved in cell proliferation or apoptosis regulation. We also established a ceRNA network to predict the regulatory effect of TP53TG1 on gene expression through miRNA. Our study highlights the essential role of lncRNA TP53TG1 in the development of cervical cancer and suggests the potential regulatory mechanisms.

ORGANISM(S): Homo sapiens

PROVIDER: GSE206471 | GEO | 2022/09/22

REPOSITORIES: GEO

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Project description:Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4-O-methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia, Caesalpinia digyna, and Flueggea leucopyrus . Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent -angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.

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LncRNA TP53TG1 plays an anti-oncogenic role in cervical cancer by synthetically regulating transcriptome profile in HeLa cells

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