Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, Changsha, Hunan, China.
Department of Neurology, School of Clinical Medicine, The First Affiliated Hospital of Guangdong Pharmaceutical University, No.19 Nonglinxia Road, Guangzhou, Guangdong, People's Republic of China.
Cell Death Dis. 2022 Aug 27;13(8):740. 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.
环状 RNA(circRNAs)是一种具有不同生物学功能的非编码 RNA。circRNAs 在癌症的进展中起着非常重要的作用。然而,许多在神经胶质瘤中circRNAs 的确切机制和功能尚不清楚。在我们的研究中,circKIF4A 被鉴定为在神经胶质瘤组织和细胞系中表达明显上调的circRNA。我们进行了功能丧失和功能获得实验,以探讨 circKIF4A 在神经胶质瘤进展中的生物学功能。我们发现,circKIF4A 的敲低显著降低了神经胶质瘤细胞的增殖和侵袭能力。此外,建立了皮下肿瘤生成模型和颅内同源神经胶质瘤注射模型,以研究 circKIF4A 在体内的功能。circKIF4A 的抑制显著增强了神经胶质瘤对替莫唑胺治疗的敏感性。circKIF4A 的过表达加速了糖酵解速率,促进了神经胶质瘤的生长和替莫唑胺耐药性。糖酵解调节酶 ALDOA 受 circKIF4A 调节,通过与神经胶质瘤细胞中 miR-335-5p 的相互作用机制。总之,我们的数据表明,circKIF4A 的上调通过结合 miR-335-5p 和上调 ALDOA 表达促进神经胶质瘤的进展。