Circ-LRP6 mediates epithelial-mesenchymal transition and autophagy in oral squamous cell carcinomas.

Abstract

BACKGROUND\nTumor metastasis seriously affects the therapeutic effect and prognosis of cancer patients. Here, we studied the role of has_circ_0000378 (circ-LRP6) in oral squamous cell carcinoma (OSCC) metastasis to explore new ideas and schemes for clinical treatment.\n\n\nMETHODS\nThe expressions of circ-LRP6 in OSCC and normal tissues from matched controls were measured by Real-Time PCR (RT-PCR). Levels of epithelial-mesenchymal transition (EMT) transcription factors, P62 and LC3B were determined by Western blot analysis and immunofluorescence (IF) assay. Furthermore, we evaluated the effects of circ-LRP6 downregulation on migration, invasion, and autophagy using CCK8, transwell assays, transmission electron microscopy (TEM), and immunofluorescence (IF) assay.\n\n\nRESULTS\nThe expression of circ-LRP6 in OSCC tissues was high. Downregulation of circ-LRP6 reduced the EMT process of SCC-15 cells, as evidenced by increased E-cadherin and decreased vimentin and Zeb1 levels. Downregulation of circ-LRP6 also decreased autophagy as shown by increased levels of P62 and decreased LC3B in SCC-15 cells. Autophagy revulsant rapamycin (RAPA) rescued the inhibitory effect of circ-LRP6 on LC3B, vimentin, and Zeb1.\n\n\nCONCLUSIONS\ncirc-LRP6 promoted EMT and autophagy of OSCC, and increased autophagy could rescue EMT in OSCC cells inhibited by circ-LRP6 siRNA.