LncRNA LINC02253 activates KRT18/MAPK/ERK pathway by mediating N6-methyladenosine modification of KRT18 mRNA in gastric cancer.

ABSTRACT

Long non-coding RNAs (lncRNAs) play a crucial role in gastric cancer (GC) progression. And understanding the role of N6-methyladenosine (m6A) in tumorigenesis is an emerging field in cancer research. Here, we identified a novel oncogene, lncRNA LINC02253, in GC. LINC02253 expression was found to be significantly increased in GC. And LINC02253 expression was closely correlated with tumor size, lymph node metastasis and TNM stage of GC. Besides, GC patients with higher LINC02253 expression had worse 5-year overall survival. Additionally, LINC02253 promoted GC cell growth, migration and invasion both in vitro and in vivo. Mechanistically, we determined that LINC02253 increased KRT18 expression through enhancing the stability of KRT18 mRNA. Furthermore, LINC02253 increased m6A modification of KRT18 mRNA to stabilize KRT18 mRNA by recruiting m6A writer METTL3. And, rescue experiments revealed that KRT18 mediated the effects of LINC02253 on growth, migration and invasion of GC cells through activating MAPK/ERK signaling pathway. In conclusion, we demonstrates that oncogenic lncRNA LINC02253 positively regulates GC growth and metastasis via increasing METTL3-mediated mRNA stability of KRT18, extending the understanding of GC pathogenesis regulated by lncRNAs.