A novel mechanism of the lncRNA PTTG3P/miR-142-5p/JAG1 axis modulating tongue cancer cell phenotypes through the Notch1 signaling.

Abstract

Tongue cancer is the most prevalent type of oral cancer. Our previous study revealed that JAG1 exerted an oncogenic effect on tongue carcinoma through the JAG1/Notch pathway. In this study, a lncRNA PTTG3P which was upregulated in tongue cancer, was found to be positively correlated with JAG1. In CAL-27 and SCC4 cells, PTTG3P silencing significantly decreased JAG1 proteins and the ability of tongue tumor cells to proliferate and migrate. PTTG3P overexpression exhibited the opposite effect on CAL-27 and SCC4 cells. PPTG3P directly bound miR-142-5p, and miR-142-5p directly bound 3'UTR of JAG1 and inhibited the expression levels of JAG1. As opposed to PTTG3P silencing, miR-142-5p inhibition increased JAG1 protein levels and tongue cancer cell proliferation and migration; moreover, miR-142-5p inhibition substantially reversed the effects of PTTG3P silencing. Finally, the PPTG3P/miR-142-5p axis regulated the level of NICD, Notch downstream c-myc, and cyclin D1, as well as EMT markers Snail, Twist, and Vimentin. In conclusion, the PTTG3P/miR-142-5p axis modulates tongue cancer aggressiveness through JAG1, potentially through a JAG1/Notch signaling pathway.