m6A modification–mediated lncRNA TP53TG1 inhibits gastric cancer progression by regulating CIP2A stability

• Published in: Cancer science Vol. 113; no. 12; pp. 4135 - 4150
• Main Authors: Fang, Deliang, Ou, Xinde, Sun, Kaiyu, Zhou, Xingyu, Li, Youpei, Shi, Peng, Zhao, Zirui, He, Yulong, Peng, Jianjun, Xu, Jianbo
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2022; John Wiley and Sons Inc
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; ALKBH5; Apoptosis; Cell cycle; Cell Line, Tumor; Cell proliferation; Cell Proliferation - genetics; CIP2A; Gastric cancer; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Hybridization; Metastases; Metastasis; N6-methyladenosine; Non-coding RNA; Original; Phosphatase; Phosphatidylinositol 3-Kinases - metabolism; Phosphoprotein phosphatase; PI3K/AKT; Protein phosphatase; Proteins; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Stomach Neoplasms - pathology; TP53TG1; Tumor suppressor genes; Tumors; Ubiquitination; ALKBH5; CIP2A; gastric cancer; TP53TG1; PI3K/AKT
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.15581

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. Reveal the important role of TP53TG1 as a tumor suppressor in inhibiting the progression of gastric cancer (GC). Explore the specific mechanism by which TP53TG1 binds to CIP2A and promotes its ubiquitination, thus inhibiting the activation of the PI3K/AKT pathway. Discover the new mechanism of TP53TG1 downregulation mediated by m6A methylation modification in GC.