CircRNA circ-PDCD11 promotes triple-negative breast cancer progression via enhancing aerobic glycolysis

Zeyu Xing,Jiaqi Liu,Xin Wang,Ruojiao Wang,Xiang Wang,Kexin Feng,Menglu Zhang

doi:10.1038/s41420-021-00604-y

Abstract

Well-described evidence has demonstrated the critical roles of aerobic glycolysis in triple-negative breast cancer (TNBC) oncotherapy. Moreover, next-generation high-throughput sequencing indicates the potential regulation of energy metabolism by circular RNAs (circRNAs) in TNBC. However, circRNA modulation of TNBC aerobic glycolysis is still unclear. Here, the present research aimed to investigate the function and underlying mechanisms of novel circPDCD11 (hsa_circ_0019853) in TNBC aerobic glycolysis. The results revealed that circPDCD11 expression was significantly upregulated in TNBC tissues and cells. Clinical data demonstrated that the high expression of circPDCD11 was closely correlated with a poor prognosis and acted as an independent risk factor for TNBC prognosis. Functionally, in vitro gain- and loss-of-function experiments revealed that circPDCD11 accelerated glucose uptake, lactate production, ATP generation, and the extracellular acidification rate in TNBC cells. In vivo, circPDCD11 silencing repressed tumor growth. Mechanistically, circPDCD11 acted as a miRNA sponge to enhance LDHA expression by sponging miR-432-5p. In conclusion, these combined results demonstrated that circPDCD11 acts as an oncogene for TNBC, providing a promising prognostic biomarker for TNBC.

Highlights

Breast cancer is a progressive malignancy that is the leading cause of cancer-related mortality in women worldwide [1]
CircRNA microarray demonstrated the high expression of circPDCD11 in triple-negative breast cancer (TNBC) To investigate the circRNA expression profile in TNBC, our team performed microarray analysis using three pairs of tissues (Fig. 1A)
Numerous circRNAs were found to be dysregulated in TNBC tissue and normal tissue

Summary

Introduction

Breast cancer is a progressive malignancy that is the leading cause of cancer-related mortality in women worldwide [1]. CircPDCD11 promoted the proliferation and aerobic glycolysis of TNBC cells through the miR-432-5p/LDHA axis. RT-qPCR demonstrated that several circRNAs were upregulated in the TNBC specimens, including circPDCD11 (Fig. 1B). 1234567890();,: Fig. 1 A circRNA microarray revealed the high expression of circPDCD11 in TNBC.

Results

Conclusion