Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, 250012, Jinan, China.
Jinan Microecological Biomedicine Shandong Laboratory and Shandong Key Laboratory of Brain Function Remodeling, 250117, Jinan, China.
Cell Death Dis. 2023 Sep 2;14(9):585. doi: 10.1038/s41419-023-06112-4.
There is an urgent need for novel diagnostic and therapeutic strategies for patients with Glioblastoma multiforme (GBM). Previous studies have shown that BCL2 like 13 (BCL2L13) is a member of the BCL2 family regulating cell growth and apoptosis in different types of tumors. However, the clinical significance, biological role, and potential mechanism in GBM remain unexplored. In this study, we showed that BCL2L13 expression is significantly upregulated in GBM cell lines and clinical GBM tissue samples. Mechanistically, BCL2L13 targeted DNM1L at the Ser616 site, leading to mitochondrial fission and high mitophagy flux. Functionally, these alterations significantly promoted the proliferation and invasion of GBM cells both in vitro and in vivo. Overall, our findings demonstrated that BCL2L13 plays a significant role in promoting mitophagy via DNM1L-mediated mitochondrial fission in GBM. Therefore, the regulation and biological function of BCL2L13 render it a candidate molecular target for treating GBM.
目前迫切需要为多形性胶质母细胞瘤（GBM）患者开发新的诊断和治疗策略。先前的研究表明，BCL2 样 13（BCL2L13）是 BCL2 家族的成员，可调节不同类型肿瘤中的细胞生长和细胞凋亡。然而，BCL2L13 在 GBM 中的临床意义、生物学作用和潜在机制仍未被探索。在这项研究中，我们发现 BCL2L13 在 GBM 细胞系和临床 GBM 组织样本中表达显著上调。从机制上讲，BCL2L13 靶向 DNM1L 的 Ser616 位点，导致线粒体分裂和高线粒体自噬通量。功能上，这些改变显著促进了体外和体内 GBM 细胞的增殖和侵袭。总的来说，我们的研究结果表明，BCL2L13 通过 DNM1L 介导的线粒体分裂在 GBM 中促进线粒体自噬，从而发挥重要作用。因此，BCL2L13 的调节和生物学功能使其成为治疗 GBM 的候选分子靶点。
