LINC00857 Interacting with YBX1 to Regulate Apoptosis and Autophagy via MET and Phosphor-AMPKa Signaling

Abstract LncRNA LINC00857 has been reported to be upregulated in lung cancer and related to poor patient survival. It can regulate cell proliferation and tumor growth in lung cancer as well as several other cancers. However, the underlying molecular mechanisms that are regulated by LINC00857 are unclear. In this study, we found that LINC00857 silencing can impair cell proliferation in 14 different genomic alterations of lung cancer cell lines. These alterations are EGFR, KRAS, TP53, MET and LKB1 mutation. The cell apoptosis and autophagy were induced upon LINC00857 silencing in lung cancer cells. Mechanistically, LINC00857 can bind to the YBX1 protein, prevent it from proteasomal degradation and increase its nuclear translocation. LINC00857 regulated MET expression via YBX1 at transcriptional level. Induced cell autophagy by LINC00857 knockdown was mainly through increased phospho-AMPKa. Collectively, LINC00857- YBX1-MET /p-AMPKa signaling is critical to regulate cell proliferation, apoptosis and autophagy, which may provide a potential clinically therapeutic target in lung cancer.