Open Access

ARTICLE

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

JIAZHUANG LI^*, WEI ZHANG, SHOUBAO GAO, LI SUN, QINGYANG TAI, YING LIU

The Second Department of Oncology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China

* Corresponding Author: Jiazhuang Li,

(This article belongs to the Special Issue: Non-Coding RNAs in the Regulation of Human Cancers)

BIOCELL 2023, 47(10), 2313-2320. https://doi.org/10.32604/biocell.2023.029860

Received 11 March 2023; Accepted 27 May 2023; Issue published 08 November 2023

Abstract

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.

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