CircTMEM87A promotes the tumorigenesis of gastric cancer by regulating the miR-1276/SLC7A11 axis

Abstract

Background: Gastric cancer (GC) is a common malignancy with high incidence and mortality, and its pathogenesis involves the regulation of circular RNAs (circRNAs). However, the molecular mechanism of circTMEM87A in GC malignant progression is uncertain.

Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of circTMEM87A, miR-1276, and solute carrier family 7 membrane 11 (SLC7A11). Western blot was applied to detect protein expression levels of EMT-related proteins (vimentin and E-cadherin) and SLC7A11. Cell counting kit-8 assay (CCK8) and thymidine analog 5-ethynyl-2'-deoxyuridine (EdU) were performed to assess cell proliferation. Apoptosis was investigated using flow cytometry. Transwell assay and wound healing assay were carried out to examine the migration of MKN-7 and AGS cells. The Cellular ROS Assay Kit, Iron Assay Kit, and GSH/GSSG Ratio Detection Assay Kit were utilized to monitor lipid ROS level, iron level, and GSH/GSSG ratio, respectively. The interaction between miR-1276 and circTMEM87A or SLC7A11 was investigated using dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. A xenograft mouse model was constructed to explore the function of circTMEM87A in tumor formation in vivo.

Results: CircTMEM87A and SLC7A11 were upregulated, while miR-1276 was downregulated in GC tissues and cells. Knockdown of circTMEM87A suppressed the proliferation and migration and promoted apoptosis and ferroptosis of GC cells. CircTMEM87A served as a sponge for miR-1276, and miR-1276 inhibitor relieved the circTMEM87A knockdown-induced effects on GC cell phenotypes. Similarly, SLC7A11, a downstream gene of miR-1276, rescued miR-1276 overexpression-induced effects on GC cell function. Furthermore, circTMEM87A knockdown inhibited GC cell tumor phenotypes in vivo.

Conclusion: CircTMEM87A promoted the proliferation and migration and inhibited apoptosis and ferroptosis of GC cells by increasing SLC7A11 expression through binding to miR-1276.

Keywords: CircTMEM87A; Ferroptosis; Gastric cancer; SLC7A11; miR-1276.