WITHDRAWN: N6-Methyladenosine Modification of PTTG3P Contributes to Colorectal Cancer Progression via IGF2BP2

Abstract

Background N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) emerged as crucial players in colorectal cancer (CRC) progression, but the m6A modified lncRNA PTTG3P in CRC are still need to be systematically defined. Methods qRT-PCR was adopted to measure the PTTG3P expression. Survival analysis was used to explore the correlation between the expression of PTTG3P and CRC patients prognosis. Receiver operating curve (ROC) was tested to evaluate the PTTG3P predictive ability. Functional studies were examined by CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay and xenograft mice model. Mechanistic studies were explored by GSEA, methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA immunoprecipitation (RIP).Results PTTG3P was upregulated in CRC and closely related to poor prognosis. Through gain and loss of function approaches, PTTG3P facilitated proliferation and glycolysis through Hippo pathway, and glycolysis inhibitor (2-DG ,3-BG) and LDHA knockdown could rescue cell proliferation. Mechanically, m6A methylation induced the elevation of PTTG3P by increasing its stability , and insulin like growth factor-2 mRNA binding proteins 2 (IGF2BP2) involved in the progression. Finally, rescue assays validated the effect of METTL3/PTTG3P/YAP1 axis in CRC progression. Conclusions m6A-induced PTTG3P could facilitates CRC development via interacting with IGF2BP2, which provides a predictive biomarker and theraperutic target for CRC.