Protective effects of all-trans retinoic acid against gastric premalignant lesions by repressing exosomal LncHOXA10-pyruvate carboxylase axis.

Abstract

Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear. We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo. Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression. Collectively, the LncHOXA10-PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.