Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, No.160 Pujian Road, Pudong New Area, Shanghai 200127, China.
Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.
ACS Chem Neurosci. 2024 Jan 17;15(2):290-299. doi: 10.1021/acschemneuro.3c00562. Epub 2023 Dec 23.
Glioma remains one of the most challenging primary brain malignancies to treat. Long noncoding RNAs (lncRNAs) and mRNAs (mRNAs) are implicated in regulating the malignant phenotypes of cancers including glioma. This study aimed to elucidate the functions and mechanisms of lncRNA LINC00265 and mRNA IFI30 in the pathogenesis of glioma. Quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed the upregulated expression of LINC00265 and IFI30 in glioma cells compared to normal human astrocytes. Western blot (WB) quantified the associated proteins. Glioma stemness and epithelial-to-mesenchymal transition (EMT) were assessed by aldehyde dehydrogenase 1 (ALDH1) activity, sphere formation, and WB. Mechanistic and rescue assays evaluated the LINC00265/miR-let-7d-5p/IFI30/ZNF384/IGF2BP2 axis. The results demonstrated that LINC00265 and IFI30 were highly expressed in glioma cells, promoting stemness and EMT. ZNF384 was identified as a transcription factor that upregulates IFI30. Moreover, LINC00265 elevated ZNF384 by sponging miR-let-7d-5p and recruiting IGF2BP2. In conclusion, LINC00265 and IFI30 act as oncogenes in glioma by driving stemness and EMT, underscoring their potential as therapeutic targets.
神经胶质瘤仍然是最难治疗的原发性脑恶性肿瘤之一。长链非编码 RNA（lncRNA）和信使 RNA（mRNA）被认为参与调节癌症的恶性表型，包括神经胶质瘤。本研究旨在阐明 lncRNA LINC00265 和 mRNA IFI30 在神经胶质瘤发病机制中的功能和机制。定量实时聚合酶链反应（RT-qPCR）分析显示，与正常人星形胶质细胞相比，神经胶质瘤细胞中 LINC00265 和 IFI30 的表达上调。Western blot（WB）定量分析相关蛋白。醛脱氢酶 1（ALDH1）活性、球体形成和 WB 评估神经胶质瘤干细胞特性和上皮间质转化（EMT）。机制和挽救试验评估了 LINC00265/miR-let-7d-5p/IFI30/ZNF384/IGF2BP2 轴。结果表明，LINC00265 和 IFI30 在神经胶质瘤细胞中高表达，促进了干细胞特性和 EMT。ZNF384 被鉴定为上调 IFI30 的转录因子。此外，LINC00265 通过海绵吸附 miR-let-7d-5p 和募集 IGF2BP2 来升高 ZNF384。总之，LINC00265 和 IFI30 通过驱动干细胞特性和 EMT 在神经胶质瘤中充当癌基因，强调它们作为治疗靶点的潜力。
