Long non-coding RNA-ATB induces trastuzumab resistance and aggravates the progression of gastric cancer by repressing miR-200c via ZNF217 elevation

Background: Trastuzumab resistance accounts for chemotherapy failure in gastric cancer patients in clinical practice. The significance of long non-coding RNAs (lncRNAs) in the maintenance of drug resistance in gastric cancer has been already underlined. Method: This study aimed to identify the specific role of lncRNA-ATB in gastric cancer progression and trastuzumab resistance. The downstream miRs of lncRNA-ATB and target genes of miRs were predicted by bioinformatics analysis and verified using dual luciferase reporter assay. Loss-and gain-function assays were performed to explore the roles of lncRNA-ATB, miR-200c, and zinc -finger protein 217 (ZNF217) in the cell functions and trastuzumab resistance of a trastuzumab-resistant gastric cancer cell line (NCI-N87-TR). Result: LncRNA-ATB was upregulated, while miR-200c was downregulated. Depletion of lncRNA-ATB or miR-200c elevation led to a decrease in malignant properties of NCI-N87-TR cells. LncRNA-ATB could negatively target miR-200c, which in turn inversely targeted and reduced the expression of ZNF217. Silencing of ZNF217 could inhibit cell viability and migration. Conclusion: lncRNA-ATB promoted the progression and trastuzumab resistance of gastric cancer by repressing miR-200c via ZNF217 upregulation.