A FoxM1/lncRNA PTTG3P/YAP1 Positive Feedback Loop Controls Colorectal Cancer Progression

Abstract

\n Background Pseudogenes are vital regulators of cancer progression. PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified. Methods qRT-PCR was adopted to measure the PTTG3P expression. Functional studies were examined by CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay and xenograft mice model. The mechanism of PTTG3P was carried by GSEA. Chromatin immunoprecipitation (ChIP) and luciferase assay were explored to certify the binding activity between PTTG3P promoter region and FoxM1. Results Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Experimental evidence discovered that PTTG3P enhanced cell proliferation and glycolysis through YAP1 and regulated FoxM1(Hippo pathway target gene). Further, LDHA knockdown or glycolysis inhibitor (2-DG,3-BG) recovered PTTG3P-induced proliferation. Mechanically, FoxM1 increase PTTG3P expression at transcription level and the PTTG3P promoter region of -900 to -1200 nt is necessary for binding with FoxM1, thus forming a positive feedback loop to facilitates the CRC progression. Additionally, FoxM1 depletion could rescue the PTTG3P function. Conclusions A FoxM1/lncRNA PTTG3P/YAP1 positive feedback loop plays a vital part in CRC progression, and targeting FoxM1, PTTG3P and YAP1 provides therapeutic targets for CRC treatment.