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N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation.
Xie, Rongjun; Liu, Longfei; Lu, Xianzhou; He, Chengjian; Yao, Hongyi; Li, Guoxin.
Afiliación
  • Xie R; Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Zhuhui District, 336, Dongfeng South Road, Hengyang, 421002, China.
  • Liu L; Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Baiyun District, 1838 Guangzhou Avenue North, Guangzhou, 510515, China.
  • Lu X; Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Zhuhui District, 336, Dongfeng South Road, Hengyang, 421002, China.
  • He C; Department of General Surgery, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Zhuhui District, 336, Dongfeng South Road, Hengyang, 421002, China.
  • Yao H; Department of Intensive Care Medicine, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Zhuhui District, 336, Dongfeng South Road, Hengyang, 421002, China.
  • Li G; Department of Intensive Care Medicine, Affiliated Nanhua Hospital, Hengyang Medical School, University of South China, Zhuhui District, 336, Dongfeng South Road, Hengyang, 421002, China.
Gastric Cancer ; 27(1): 49-71, 2024 Jan.
Article en En | MEDLINE | ID: mdl-37897508
BACKGROUND: Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. METHODS: OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. RESULTS: In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. CONCLUSIONS: In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / MicroARNs Límite: Humans Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Japón
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / MicroARNs Límite: Humans Idioma: En Revista: Gastric Cancer Asunto de la revista: GASTROENTEROLOGIA / NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Japón