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Published on: May 10, 2024
m6A modification-mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability
Deliang Fang1,2, Xinde Ou1,2, Kaiyu Sun1
1Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Abstract:
Long noncoding RNAs (lncRNAs) are associated with various types of cancer. However, the precise roles of many lncRNAs in tumor progression remain unclear. In this study, we found that the expression of the lncRNA TP53TG1 was downregulated in gastric cancer (GC) and it functioned as a tumor suppressor. In addition, low TP53TG1 expression was significantly associated with poor survival in patients with GC. TP53TG1 inhibited the proliferation, metastasis, and cell cycle progression of GC cells, while it promoted their apoptosis. m6A modification sites are highly abundant on TP53TG1, and demethylase ALKBH5 reduces TP53TG1 stability and downregulates its expression. TP53TG1 interacts with cancerous inhibitor of protein phosphatase 2A (CIP2A) and triggers its ubiquitination-mediated degradation, resulting in the inhibition of the PI3K/AKT pathway. These results suggest that TP53TG1 plays an important role in inhibiting the progression of GC and provides a crucial target for GC treatment.
Insights
The long noncoding RNA TP53TG1 acts as a tumor suppressor in gastric cancer (GC). Its downregulation promotes GC progression, offering a potential therapeutic target for this disease.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long noncoding RNAs (lncRNAs) are implicated in cancer, but their specific roles in tumor progression are often unknown.
- Gastric cancer (GC) remains a significant health concern with a need for novel therapeutic targets.
Purpose of the Study:
- To investigate the role of the lncRNA TP53TG1 in gastric cancer.
- To elucidate the molecular mechanisms underlying TP53TG1's function in GC progression.
Main Methods:
- Quantitative analysis of TP53TG1 expression in GC tissues and cell lines.
- Functional assays to assess the impact of TP53TG1 on GC cell proliferation, migration, invasion, cell cycle, and apoptosis.
- Investigation of the regulatory role of ALKBH5 on TP53TG1 stability and expression.
- Analysis of TP53TG1 interaction with CIP2A and its effect on the PI3K/AKT pathway.
Main Results:
- TP53TG1 expression was significantly downregulated in GC tissues and correlated with poor patient survival.
- Overexpression of TP53TG1 suppressed GC cell proliferation, metastasis, and cell cycle progression, while promoting apoptosis.
- ALKBH5 was found to destabilize TP53TG1, leading to its reduced expression.
- TP53TG1 induced the degradation of CIP2A, consequently inhibiting the PI3K/AKT signaling pathway.
Conclusions:
- TP53TG1 functions as a tumor suppressor in gastric cancer.
- The ALKBH5-TP53TG1-CIP2A axis regulates GC progression via the PI3K/AKT pathway.
- TP53TG1 represents a promising therapeutic target for gastric cancer treatment.
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