Circ_0007099 upregulates GNG7 to function as a tumor inhibitor in gastric carcinoma by interacting with miR-425-3p

Zhipeng Zhang; Yikai Zhou; Na Zhou; Junda Yin; Xuechun Kuang

doi:10.21037/jgo-22-684

Circ_0007099 upregulates GNG7 to function as a tumor inhibitor in gastric carcinoma by interacting with miR-425-3p

J Gastrointest Oncol. 2022 Aug;13(4):1626-1639. doi: 10.21037/jgo-22-684.

Authors

Zhipeng Zhang^#¹, Yikai Zhou^#¹, Na Zhou^{2

3}, Junda Yin¹, Xuechun Kuang^{1

3}

Affiliations

¹ Department of Geratology Surgery, Xiangya Hospital, Central South University, Changsha, China.
² Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China.
³ Teaching and Research Section of Clinical Nursing, Xiangya Hospital, Central South University, Changsha, China.

^# Contributed equally.

Abstract

Background: Circular RNAs (circRNAs) are usually dysregulated in human tumors and affect the malignant progression of tumors. Circ_0007099 is known to be downregulated in gastric carcinoma (GC), and this research was performed to investigate the regulatory function of circ_0007099 in GC progression.

Methods: The detection of circ_0007099, miR-425-3p, and G protein γ subunit 7 (GNG7) was performed via reverse transcription-quantitative polymerase chain reaction assay. Cell proliferation was determined by EdU and colony formation assays, and angiogenesis was assessed via a tube formation assay. Glucose metabolism was evaluated with commercial kits, and protein expression was measured by western blot. Dual-luciferase reporter and RNA immunoprecipitation assays were performed to validate the target interaction. An in vivo exploration of circ_0007099 was conducted using a xenograft tumor assay.

Results: Circ_0007099 was downregulated in GC patients and cells. Overexpression of circ_0007099 repressed cell proliferation, angiogenesis, and glucose metabolism while enhancing apoptosis in GC cells. Circ_0007099 exhibited a sponge effect on miR-425-3p, and the anti-tumor function of circ_0007099 was achieved by sponging miR-425-3p. Furthermore, miR-425-3p directly targeted GNG7, and miR-425-3p inhibition suppressed malignant progression by reducing GNG7 expression in GC cells. Circ_0007099 sponged miR-425-3p to upregulate the level of GNG7. We also found that in vivo tumor growth was reduced by circ_0007099 mediating the miR-425-3p/GNG7 axis.

Conclusions: This study demonstrated that circ_0007099 inhibits the malignant behavior of GC cells by binding to miR-425-3p, thus regulating the expression of GNG7.

Keywords: Circ_0007099; GNG7; gastric cancer; miR-425-3p.