Lnc-TPT1-AS1/CBP/ATIC Axis Mediated Purine Metabolism Activation Promotes Breast Cancer Progression

Abstract

The purine biosynthetic pathway was recently identified to play a crucial role in breast cancer progression. However, little was known about the regulatory mechanisms of long non-coding RNA in breast cancer purine metabolism. In this study, we discovered that LncRNA TPT1-AS1 (TPT1-AS1) was downregulated in breast cancer tissues. Its introduction in breast cancer cells markedly suppressed tumor growth and metastasis in xenograft tumor models. Mass spectrometric analysis suggested that the purine biosynthetic pathway was activated in TPT1-AS1-knockdown MCF-7 cells. Inosine monophosphate (IMP), the product of de novo purine biosynthesis, was significantly upregulated. Mechanistically, we found that TPT1-AS1 could physically interact with CBP (CREB-binding protein), which consequently led to the loss of H3K27Ac in the promoter area of ATIC, the key enzyme of IMP synthesis. This process could block breast cancer purine metabolism and inhibit breast cancer progression. In conclusion, our findings illustrate the role of non-coding RNAs in breast cancer purine metabolism reprogramming and present a potential candidate for breast cancer therapy.