Department of Pathology, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, China.
Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai, China.
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1261-7. doi: 10.1016/j.bbrc.2014.03.105. Epub 2014 Mar 29.
Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n=60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment.
先前本实验室的研究表明，微小 RNA-21（miR-21）有助于胶质母细胞瘤（GBM）细胞对依托泊苷（一种 II 型拓扑异构酶抑制剂）的化疗耐药性。我们还表明，LRRFIP1 是 miR-21 的靶标。在这项研究中，我们发现人 GBM 组织中较高的基线 LRRFIP1 表达（n=60）与随后接受依托泊苷治疗时的更好预后相关。在培养的 U373MG 细胞中的实验表明，转染导致 LRRFIP1 过表达的载体的 U373MG 细胞对依托泊苷的毒性增强（与转染对照载体的细胞相比）。裸鼠实验表明，LRRFIP1 过表达的异种移植物对依托泊苷的反应更好。这些发现表明，GBM 中较高的基线 LRRFIP1 表达与对依托泊苷的更好反应相关，并鼓励探索 LRRFIP1 作为 GBM 治疗的靶标。
