The long non-coding RNA MACC1-AS1 promotes nasopharyngeal carcinoma cell stemness via suppressing miR-145-mediated inhibition on SMAD2/MACC1-AS1 axis

Abstract

The promoting roles of the long non-coding RNA (lncRNA) MACC1-AS1 have been indicated in gastric and pancreatic cancer, however, its roles in nasopharyngeal carcinoma (NPC) progression are never been revealed. In this work, it was shown that lncRNA MACC1-AS1 was highly expressed in NPC tissues and cells relative to the adjacent tissues and nasal mucosa cells, respectively. Additionally, MACC1-AS1 expression was positively correlated with the high rate of lymph node metastasis and large tumor size. in vitro and in vivo experiments revealed that MACC1-AS1 knockdown reduced the stemness of NPC cells, which was indicated by the decrease of sphere-forming ability, ALDH1 activity, stemness marker expression and tumor-initiating capacity. Mechanistic research showed that MACC1-AS1 antagonized the activity of miR-145, which could target Smad2. In turn, smad2 directly bound to MACC1-AS1 promoter and thus increased MACC1-AS1 expression. Notably, knockdown of miR-145 or overexpression of Smad2 rescued the inhibition of MACC1-AS1 knockdown on the stemness of NPC cells. Therefore, these results demonstrate a novel MACC1-AS1/miR-145/Smad2 negative loop responsible for NPC cell stemness.

Keywords: Long non-coding RNA; MACC1-AS1; Nasopharyngeal carcinoma; Smad2; Stemness; miR-145.