LncRNA LINC00470 promotes the degradation of PTEN mRNA to facilitate malignant behavior in gastric cancer cells

摘要

Gastric cancer (GC) is the fourth most frequent malignancy worldwide. Recently, long noncoding RNA (lncRNA) LINC00470 has been demonstrated to play an oncogenic role in human cancer. However, the clinical significance and functional role of LINC00470 in the progression of GC is largely unknown. In this study, our findings showed that LINC00470 was significantly upregulated in GC tissues and cell lines, and correlated with distant metastasis, TNM stage and poor prognosis. Overexpression and knockdown experiments revealed its oncogenic functions on GC cell proliferation, migration and invasion. Mechanistically, LINC00470 associated with PTEN mRNA and suppressed its stability through interaction with the N-6-methyladenosine (m(6)A) writer METTL3. We also showed that LINC00470-METTL3-mediated PTEN mRNA degradation relied on the m(6)A reader protein YTHDF2-dependent pathway. Taken together, LINC00470 might serve as a therapeutic target for GC patients. (C) 2019 Elsevier Inc. All rights reserved.