The regulatory relationship and function of LncRNA FAM225A-miR-206-ADAM12 in gastric cancer

Nan Chen; Xuedan Zhu; Yinxing Zhu; Junfeng Shi; Juan Zhang; Cuiju Tang; Jinfei Chen

The regulatory relationship and function of LncRNA FAM225A-miR-206-ADAM12 in gastric cancer

Am J Transl Res. 2021 Aug 15;13(8):8632-8652. eCollection 2021.

Authors

Nan Chen¹, Xuedan Zhu¹, Yinxing Zhu¹, Junfeng Shi¹, Juan Zhang¹, Cuiju Tang¹, Jinfei Chen²

Affiliations

¹ Department of Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, Jiangsu, China.
² Cancer Center, Taikang Xianlin Drum Tower Hospital, Nanjing University School of Medicine Nanjing, Jiangsu, China.

PMID: 34539984
PMCID: PMC8430187

Abstract

Objective: To investigate the role and functions of FAM225A in gastric cancer.

Methods: The expressions of FAM225A, miR-206, ADAM12 and epithelial-mesenchymal transition (EMT)-related genes were detected by quantitative real-time PCR and Western blot. Functional experiments including cell counting kit-8, colony formation, wound-healing, and Transwell assays were conducted to analyze the biological characteristics of gastric cancer cells in different groups. Bioinformatics, dual-luciferase reporter assay and Pearson correlation coefficients were performed for determining the regulatory relationship of lncRNA-miRNA-mRNA. In vivo nude mouse xenografts and immunohistochemistry were used to verify the results in vitro.

Results: In gastric cancer, FAM225A and ADAM12 expressions were up-regulated, while miR-206 expression was down-regulated. Opposite to the regulatory effects of overexpressed FAM225A, blocking FAM225A expression reduced cell viability, migration, invasion and number of cell clones, increased E-Cadherin expression, inhibited N-Cadherin and Vimentin expressions, and ultimately promoted tumor growth. MiR-206 inhibitor partially offset the effects of siFAM225A. Moreover, FAM225A competitively bound to miR-206 to up-regulate ADAM12 expression. Overexpressed ADAM12 partially reversed the effect of miR-206 mimic on the biological characteristics of gastric cancer cells and EMT-related proteins.

Conclusion: Our research revealed that FAM225A-miR-206-ADAM12 axis may be a potential pathway for regulating gastric cancer.

Keywords: ADAM12; Gastric cancer; lncRNA FAM225A; miR-206; proliferation.