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  • Title: LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/β-catenin signaling.
    Author: Guan B, Ma J, Yang Z, Yu F, Yao J.
    Journal: Environ Toxicol; 2021 Aug; 36(8):1640-1653. PubMed ID: 33974352.
    Abstract:
    Long noncoding RNAs (lncRNAs) exert crucial effects on the development of many malignancies, including gastric cancer. Herein, we investigated the role of lncRNA noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) divergent transcript (NCK1-DT, also known as NCK1-AS1) in gastric cancer. Reverse transcription quantitative polymerase chain reaction demonstrated that NCK1-AS1 exhibited high expression in gastric cancer tissues and cells. In vitro assays including MTT, colony formation, Transwell, wound healing and sphere formation assays indicated that NCK1-AS1 depletion inhibited cell proliferation, migration, invasion and stemness maintenance. Luciferase reporter and RIP assays suggested that NCK1-AS1 functioned as a competitive endogenous RNA (ceRNA) for miR-22-3p to positively modulate BCL9 expression. BCL9 was a target gene of miR-22-3p. According to western blot analysis and TOP/FOP flash assay, NCK1-AS1 activated the Wnt/β-catenin signaling via the miR-22-3p/BCL9 axis. Furthermore, rescue experiments verified that NCK1-AS1 affected cellular processes by activating the Wnt/β-catenin signaling pathway via the miR-22-3p/BCL9 axis. Tumor xenograft model validated that NCK1-AS1 promoted tumor growth in vivo via the Wnt/β-catenin signaling by upregulating BCL9 expression. Overall, NCK1-AS1 functions as an oncogene and promotes gastric cancer progression via the miR-22-3p/BCL9-Wnt/β-catenin signaling pathway.
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