Circular RNA circRNF20 promotes breast cancer tumorigenesis and Warburg effect through miR-487a/HIF-1α/HK2

• Published in: Cell death & disease 2020-02, Vol.11 (2), p.145-10, Article 145
• Main Authors: Cao, Lili, Wang, Min, Dong, Yujin, Xu, Bo, Chen, Ju, Ding, Yu, Qiu, Shusheng, Li, Liang, Karamfilova Zaharieva, Elena, Zhou, Xinwen, Xu, Yanbin
• Format: Article
• Language: English
• Subjects: 13/1; 13/2; 13/44; 13/89; 3' Untranslated Regions; 631/67/1347; 631/80/221; Animals; Antibodies; Binding Sites; Biochemistry; Biomedical and Life Sciences; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell Biology; Cell Culture; Cell Proliferation; Circular RNA; DNA microarrays; Female; Gene Expression Regulation, Neoplastic; Glycolysis; Hexokinase; Hexokinase - genetics; Hexokinase - metabolism; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factors; Immunology; Life Sciences; Male; MCF-7 Cells; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; Middle Aged; miRNA; RNA, Circular - genetics; RNA, Circular - metabolism; Signal Transduction; Transcription; Transcription, Genetic; Tumorigenesis; Warburg Effect, Oncologic
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2336-0

Compelling evidence has demonstrated the potential functions of circular RNAs (circRNAs) in breast cancer (BC) tumorigenesis. Nevertheless, the underlying mechanism by which circRNAs regulate BC progression is still unclear. The purpose of present research was to investigate the novel circRNA circRNF20 (hsa_circ_0087784) and its role in BC. CircRNA microarray sequencing revealed that circRNF20 was one of the upregulated transcripts in BC samples. Increased circRNF20 level predicted the poor clinical outcome in BC specimens. Functionally, circRNF20 promoted the proliferation and Warburg effect (aerobic glycolysis) of BC cells. Mechanistically, circRNF20 harbor miR-487a, acting as miRNA sponge, and then miR-487a targeted the 3’-UTR of hypoxia-inducible factor-1α (HIF-1α). Moreover, HIF-1α could bind with the promoter of hexokinase II (HK2) and promoted its transcription. In conclusion, this finding illustrates the vital roles of circRNF20 via the circRNF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.