Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3

Abstract

Homeobox D gene cluster antisense growth-associated long noncoding RNA (HAGLR) functions as a crucial regulator in the progression and development of human cancers. We analyzed effects of HAGLR, microRNA (miR)-143-5p and lysosome-associated membrane glycoprotein (LAMP)3 on esophageal cancer (EC) and the related mechanisms. Microarray analysis was used to screen out EC-related genes and the regulation network among HAGLR, miR-143-5p, and LAMP3. The regulatory mechanisms of HAGLR and miR-143-5p in EC were analyzed following the treatment of miR-143-5p mimic, miR-143-5p inhibitor, HAGLR vector, or small interfering RNA against HAGLR in EC cells. The expression of N-cadherin, vimentin, Twist1, Snail1, and E-cadherin as well as the abilities of cell proliferation, invasion, and migration were measured. The effects of the HAGLR/miR-143-5p/LAMP3 axis were determined in vivo by assessing tumor formation in nude mice. The expression of HAGLR and LAMP3 was increased, whereas that of miR-143-5p was diminished in EC tissues and cells. HAGLR could competitively bind to miR-143-5p, and miR-143-5p targeted LAMP3. Down-regulated HAGLR or up-regulated miR-143-5p increased E-cadherin expression and significantly diminished expression of LAMP3, N-cadherin, vimentin, Twist1, and Snail1. Moreover, down-regulated HAGLR inhibited cell proliferation, invasion, migration, epithelial-mesenchymal transition (EMT), and tumor growth. Moreover, down-regulation of HAGLR inhibited LAMP3 expression by sponging miR-143-5p, thereby suppressing the progression of EC. Taken together, our results suggest HAGLR acts as a competing endogenous RNA of miR-143-5p to increase the expression of LAMP3, thus promoting EMT, proliferation, invasion, and migration in EC cells.—Yang, C., Shen, S., Zheng, X., Ye, K., Sun, Y., Lu, Y., Ge, H. Long noncoding RNA HAGLR acts as a microRNA-143-5p sponge to regulate epithelial-mesenchymal transition and metastatic potential in esophageal cancer by regulating LAMP3. FASEB J. 33, 10490–10504 (2019). www.fasebj.org.