LncRNA NCK1-AS1 exerts oncogenic property in gastric cancer by targeting the miR-22-3p/BCL9 axis to activate the Wnt/β-catenin signaling

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/beta-catenin signaling via the miR-22-3p/BCL9 axis. Furthermore, rescue experiments verified that NCK1-AS1 affected cellular processes by activating the Wnt/beta-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/beta-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/beta-catenin signaling pathway.

Automated summary

The lncRNA NCK1-AS1 is highly expressed in gastric cancer and acts as an oncogene by competitively binding to miR-22-3p to upregulate BCL9 expression, leading to the activation of the Wnt/β-catenin signaling pathway and promoting gastric cancer progression.