Int J Biol Sci 2022; 18(2):841-857. doi:10.7150/ijbs.66114 This issue
1. School of Basic Medical Science, Central South University, Changsha 410013, Hunan, China.
2. Cancer Research Institute, Central South University, Changsha 410013, Hunan, China.
3. Armed Police Hospital of Hunan Province, Changsha 410013, Hunan, China.
4. Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha 410013, Hunan, China.
5. Department of Clinical Laboratory, Yueyang Central Hospital, Yueyang 414000, Hunan, China.
#These authors contributed equally to this work.
CircRNAs have garnered significant interest in recent years due to their regulation in human tumorigenesis, yet, the function of most glioma-related circRNAs remains unclear. In this study, using RNA-Seq, we screened differentially regulated circRNAs in glioma, in comparison to non-tumor brain tissue. Loss- and gain-of-function strategies were used to assess the effect of circCDK14 on tumor progression both in vitro and in vivo. Luciferase reporter, RNA pull-down and fluorescence in situ hybridization assays were carried out to validate interactions between circCDK14 and miR-3938 as well as miR-3938 and PDGFRA. Transmission electron microscopic observation of mitochondria, iron and reactive oxygen species assays were employed for the detection of circCDK14 effect on glioma cells' sensitivity to erastin-induced ferroptosis (Fp). Our findings indicated that circCDK14 was overexpressed in glioma tissues and cell lines, and elevated levels of circCDK14 induced poor prognosis of glioma patients. CircCDK14 promotes the migration, invasion and proliferation of glioma cells in vitro as well as tumorigenesis in vivo. An evaluation of the underlying mechanism revealed that circCDK14 sponged miR-3938 to upregulate oncogenic gene PDGFRA expression. Moreover, we also found that circCDK14 reduced glioma cells' sensitivity to Fp by regulating PDGFRA expression. In conclusion, circCDK14 induces tumor in glioma and increases malignant tumor behavior via the miR-3938/PDGFRA axis. Hence, the miR-3938/PDGFRA axis may be an excellent candidate of anti-glioma therapy.
Keywords: CircCDK14, Glioma, miR-3938, PDGFRA, Ferroptosis