Background Long noncoding RNAs (lncRNAs) play critical factors in tumor progression and are ectopically expressed in malignant tumors. Until now, lncRNA PTTG3P biological function in colorectal cancer (CRC) needs further to be clarified.
Methods qRT-PCR was used to measure the PTTG3P level and CCK-8, glucose uptake, lactate assay, ATP assay, ECAR assay, and xenograft mice model were adopted to evaluate the glycolysis and proliferation, and macrophage polarization were determined in CRC cells. Xenograft experiments were utilized to analyze tumor growth.
Results Ectopic expression of PTTG3P was involved in CRC and related to dismal prognosis. Through gain-of-function and loss-of-function approaches, PTTG3P enhanced cell proliferation and glycolysis through YAP1. Further, LDHA knockdown or glycolysis inhibitor (2-DG,3-BG) recovered PTTG3P-induced proliferation. And PTTG3P overexpression could facilitate M2 polarization of macrophages. Silenced PTTG3P decreased the level of inflammatory cytokines TNF-α, IL-1β, and IL-6, and low PTTG3P expression related with CD8+ T, NK, and TFH cell infiltration. Besides, HIF1A could increase PTTG3P expression by binding to the PTTG3P promoter region.
Conclusions Hypoxia-induced PTTG3P contributes to glycolysis and M2 phenotype of macrophage, which proposes a novel approach for clinical treatment.