WITHDRAWN: A Novel Axis HIF1A/miR-1271-5p/lncRNA PTTG3P/YAP1 Contributes to Colorectal Cancer Progression and Relates to an Immune-Suppressing Microenvironment

Abstract

Background Pseudogene has emerged as key regulators of important biological processes involved in human cancers. However, the PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified. Methods qRT-PCR was adopted to measure the PTTG3P expression in different cell line and CRC tissues. Cellular localization of PTTG3P was detected by subcellular fractionation assay. In vitro and in vivo experiments were carried out to explore the bioeffect of PTTG3P in CRC cells. Chromatin immunoprecipitation (ChIP), luciferase assay and RIP were explored to certify the direct binding of PTTG3P and microRNA. 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 YAP1, and glycolysis inhibitor (2-DG,3-BG) and LDHA knockdown could rescue cell proliferation and tumorigenesis. Mechanically, miR-1271-5p modulates PTTG3P expression and miR-1271-5p mimics could recover the PTTG3P function. Also HIF1A increased PTTG3P expression in both normoxia and hypoxia conditions by ameliorating miR-1271-5p expression. In addition, silencing PTTG3P decreases the level of inflammatory cytokines TNF-α, IL-1β and IL-6, and low PTTG3P expression relates with CD8+ T, NK and TFH cells infiltration. Conclusions Our findings verified the oncogenic function of PTTG3P in assisting the cell proliferation and glycolysis, demonstrating the pivotal roles of HIF1A/miR-1271-5p/lncRNA PTTG3P/YAP1 in CRC progression, which proposes a novel approach for clinical treatment.