Novel circular RNA circSLIT2 facilitates the aerobic glycolysis of pancreatic ductal adenocarcinoma via miR-510-5p/c-Myc/LDHA axis

• Published in: Cell death & disease 2021-06, Vol.12 (7), p.645-9, Article 645
• Main Authors: Guan, Hua, Luo, Wei, Liu, Yuping, Li, Mingfei
• Format: Article
• Language: English
• Subjects: 13/2; 13/31; 13/44; 13/89; 14/1; 38/43; 38/47; 631/67/2327; 692/699/67/2327; Adenocarcinoma; Aged; Animals; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; c-Myc protein; Cancer; Carcinogenesis; Carcinoma, Pancreatic Ductal - enzymology; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - pathology; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Proliferation; Circular RNA; Datasets; Experiments; Fatalities; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycolysis; Humans; Immunology; L-Lactate dehydrogenase; L-Lactate Dehydrogenase - genetics; L-Lactate Dehydrogenase - metabolism; Lactic acid; Life Sciences; Male; Medical prognosis; Metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; Myc protein; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - enzymology; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Proto-Oncogene Proteins c-myc - genetics; Proto-Oncogene Proteins c-myc - metabolism; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Transcription; Transcription, Genetic; Tumorigenesis
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03918-y

Increasing evidence has indicated the great diagnostic and therapeutic potentials of circular RNAs (circRNAs) in human cancers. Although the biological roles of circRNAs in pancreatic ductal adenocarcinoma (PDAC) have been partially annotated, the potential regulatory mechanism of circRNAs in PDAC tumorigenesis remains poorly understood. Here, our study found that the novel circRNA circSLIT2 was significantly upregulated in PDAC tissues and cells. Clinically, ectopic high-expression of circSLIT2 was correlated with unfavorable prognosis of PDAC patients. Functional experiments demonstrated that circSLIT2 promoted the aerobic glycolysis and proliferation of PDAC cells in vitro, and circSLIT2 knockdown inhibited tumor growth in vivo. Mechanistically, circSLIT2 acted as miRNA sponge to target miR-510-5p/c-Myc axis. Furthermore, c-Myc bound with the promoter region of lactate dehydrogenase A (LDHA) to activate the transcription. Collectively, present findings reveal that circSLIT2/miR-510-5p/c-Myc/LDHA axis participates in the aerobic glycolysis and carcinogenesis of PDAC, and may act as a promising therapeutic target.