Circular RNA circSLC25A16 contributes to the glycolysis of non-small-cell lung cancer through epigenetic modification

Hong Shangguan,Tian Tian,Dongxiao Lv,Hong Feng,Xingwen Wang,Junfei Wang

doi:10.1038/s41419-020-2635-5

Abstract

Growing evidence has highlighted the roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC), however, their roles in NSCLC glycolysis remains poorly understood. CircRNAs microarray profiles discovered a novel exon-derived circRNA, circSLC25A16 (hsa_circ_0018534), in NSCLC tissue samples. In NSCLC samples, high-expression of circSLC25A16 was associated with unfavorable prognosis. Cellular experiments revealed that circSLC25A16 accelerated the glycolysis and proliferation of NSCLC cells. Besides, circSLC25A16 knockdown repressed the in vivo growth by xenograft assays. RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that circSLC25A16 and miR-488-3p were both located in cytoplasm. Mechanistic experiments demonstrated that circSLC25A16 interacts with miR-488-3p/HIF-1α, which activates lactate dehydrogenase A (LDHA) by facilitating its transcription. Collectively, present research reveals the crucial function of circSLC25A16 on NSCLC glycolysis through miR-488-3p/HIF-1α/LDHA, suggesting the underlying pathogenesis for NSCLC and providing a therapeutic strategy for precise treatment.

Highlights

Non-small-cell lung cancer (NSCLC) takes the largest proportion of lung cancer, the most common type of cancer, and acts as the leading cause of cancer-related mortality worldwide[1,2]
CircSLC25A16 was upregulated in the NSCLC Using the circRNA microarray, our team found that a series of circRNAs were dysregulated in the NSCLC tissue samples and non-tumor normal tissue (Fig. 1a)
We found that the newfound circRNA, named as circ circSLC25A16, was significantly upregulated in the NSCLC tissue and cells

Summary

Introduction

Non-small-cell lung cancer (NSCLC) takes the largest proportion of lung cancer, the most common type of cancer, and acts as the leading cause of cancer-related mortality worldwide[1,2]. The incidence and mortality of NSCLC have been increased and traditional surgical resection is difficult to comprehensively overcome the puzzle[3]. On this basis, the chemotherapy and more accurate molecular targeting therapy are more necessary. In spite of current advances in therapy, the overall five-year survival rate for NSCLC patient still remains poor[4]. Novel diagnostic approach and therapeutic target are urgently necessary to optimize the prognosis and therapeutic effect

Methods

Results

Conclusion