CircKIF4A promotes glioma growth and temozolomide resistance by accelerating glycolysis

• Published in: Cell death & disease 2022-08, Vol.13 (8), p.740-11, Article 740
• Main Authors: Luo, Kui, Liu, Aiqun, Wu, Hao, Liu, Qiang, Dai, Jin, Liu, Yu, Wang, Zhifei
• Format: Article
• Language: English
• Subjects: 13; 13/89; 38; 38/89; 631/337/384; 631/67/1922; 82; 82/80; 96; 96/95; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Brain cancer; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Breast cancer; Cell Biology; Cell Culture; Cell Line, Tumor; Cell lines; Cell Movement; Cell Proliferation; Chemotherapy; Disease; Drug Resistance, Neoplasm; Enzymes; Experiments; Fructose-Bisphosphate Aldolase - metabolism; Gene Expression Regulation, Neoplastic; Glioma; Glioma - metabolism; Glioma - pathology; Glioma cells; Glycolysis; Hospitals; Humans; Immunology; Kinesins; Life Sciences; Liver cancer; MicroRNAs - genetics; Proteins; RNA, Circular - genetics; Temozolomide; Tumorigenesis; Tumors
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-022-05175-z

Circular RNAs (circRNAs) are a kind of noncoding RNAs that have different biological functions. CircRNAs play very important parts in the progression of cancers. Nevertheless, the exact mechanism and function of many circRNAs in glioma are not clear. In our study, circKIF4A was identified as a remarkably upregulated circRNA expressed in glioma tissues and cell lines. We performed loss-off function and gain-of-function experiments to inquire into the biological function of circKIF4A in the progression of glioma. We discovered that knockdown of circKIF4A remarkably decreased the proliferation and invasion ability of glioma cells. Moreover, subcutaneous tumorigenesis model and intracranial injection of orthotopic glioma model were established to investigate the functions of circKIF4A in vivo. Suppression of circKIF4A remarkably enhanced the sensitivity of glioma to temozolomide treatment. The glycolysis rate was accelerated by circKIF4A overexpression, which promoted glioma growth and temozolomide resistance. The glycolysis regulating enzyme ALDOA was regulated by circKIF4A through the mechanism of interactivity with miR-335-5p in glioma cells. In a word, our data showed that the upregulation of circKIF4A facilitates glioma progression by means of binding miR-335-5p and upregulating ALDOA expression.