Li Suwen, Yuan Jiaqi, Cheng Zhe, Li Yongdong, Cheng Shan, Liu Xinglei, Huang Shilu, Xu Zhipeng, Wu Anyi, Liu Liang, Dong Jun
Department of Neurosurgery, the Second Affiliated Hospital of Soochow University, Suzhou, China.
Department of Neurosurgery, the Zhangjiagang Hospital of Traditional Chinese Medicine, Suzhou, China.
Cell Death Discov. 2024 Feb 10;10(1):71. doi: 10.1038/s41420-024-01841-7.
Abnormal lipid metabolism is an essential hallmark of glioblastoma. Hormone sensitive lipase (HSL), an important rate-limiting enzyme contributed to lipolysis, which was involved in aberrant lipolysis of glioblastoma, however, its definite roles and the relevant regulatory pathway have not been fully elucidated. Our investigations disclosed high expression of HSL in glioblastoma. Knock-down of HSL restrained proliferation, migration, and invasion of glioblastoma cells while adding to FAs could significantly rescue the inhibitory effect of si-HSL on tumor cells. Overexpression of HSL further promoted tumor cell proliferation and invasion. Bioinformatics analysis and dual-luciferase reporter assay were performed to predict and verify the regulatory role of ncRNAs on HSL. Mechanistically, hsa_circ_0021205 regulated HSL expression by sponging miR-195-5p, which further promoted lipolysis and drove the malignant progression of glioblastoma. Besides, hsa_circ_0021205/miR-195-5p/HSL axis activated the epithelial-mesenchymal transition (EMT) signaling pathway. These findings suggested that hsa_circ_0021205 promoted tumorigenesis of glioblastoma through regulation of HSL, and targeting hsa_circ_0021205/miR-195-5p/HSL axis can serve as a promising new strategy against glioblastoma.
异常脂质代谢是胶质母细胞瘤的一个重要标志。激素敏感性脂肪酶(HSL)是一种参与脂解的重要限速酶,其参与了胶质母细胞瘤的异常脂解过程,然而,其确切作用和相关调控途径尚未完全阐明。我们的研究发现胶质母细胞瘤中HSL表达较高。敲低HSL可抑制胶质母细胞瘤细胞的增殖、迁移和侵袭,而添加脂肪酸可显著挽救si-HSL对肿瘤细胞的抑制作用。HSL的过表达进一步促进肿瘤细胞的增殖和侵袭。进行了生物信息学分析和双荧光素酶报告基因检测以预测和验证非编码RNA对HSL的调控作用。机制上,hsa_circ_0021205通过吸附miR-195-5p来调节HSL表达,这进一步促进了脂解并推动了胶质母细胞瘤的恶性进展。此外,hsa_circ_0021205/miR-195-5p/HSL轴激活了上皮-间质转化(EMT)信号通路。这些发现表明hsa_circ_0021205通过调节HSL促进了胶质母细胞瘤的肿瘤发生,靶向hsa_circ_0021205/miR-195-5p/HSL轴可作为一种有前景的抗胶质母细胞瘤新策略。