Department of Orthopedic Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
J Orthop Res. 2024 Feb;42(2):443-452. doi: 10.1002/jor.25689. Epub 2023 Oct 2.
Fusion genes have been implicated in the development and progression of several types of sarcomas, serving as valuable diagnostic and prognostic markers, as well as potential therapeutic targets. We discovered a novel major facilitator superfamily domain-containing 7 (MFSD7) and adenosine triphosphate 5I (ATP5I) gene fusion from sarcomas. In this study, the MFSD7-ATP5I fusion transcript was screened using RNA sequencing in 55 sarcoma samples and sixteen normal samples. The MFSD7-ATP5I fusion transcript was detected in 58% of sarcoma samples. The correlation between the expression of MFSD7-ATP5I fusion transcript and clinicopathological information was analyzed, and MFSD7-ATP5I expression is associated with marked pleomorphism and lower tumor necrosis. Cell migration and invasion was significantly reduced by knock-down of MFSD7-ATP5I. Cell migration and invasion was increased by overexpression of MFSD7-ATP5I. A phosphokinase assay demonstrated that MFSD7-ATP5I is involved in the GSK-3 pathway. The current study found that MFSD7-ATP5I is associated with increasing pleomorphism and decreasing necrosis of tumors. And our gain and loss of function experiments prove that MFSD7-ATP5I promotes the invasiveness of tumor cells.
融合基因与多种肉瘤的发生和发展有关，可作为有价值的诊断和预后标志物，以及潜在的治疗靶点。我们从肉瘤中发现了一种新型的主要易化超家族结构域包含 7 号（MFSD7）和三磷酸腺苷 5I 型（ATP5I）基因融合。在这项研究中，我们使用 RNA 测序在 55 个肉瘤样本和 16 个正常样本中筛选 MFSD7-ATP5I 融合转录本。MFSD7-ATP5I 融合转录本在 58%的肉瘤样本中被检测到。分析了 MFSD7-ATP5I 融合转录本的表达与临床病理信息之间的相关性，并且 MFSD7-ATP5I 的表达与显著的多形性和较低的肿瘤坏死相关。敲低 MFSD7-ATP5I 显著降低了细胞迁移和侵袭。过表达 MFSD7-ATP5I 增加了细胞迁移和侵袭。磷酸激酶测定表明 MFSD7-ATP5I 参与 GSK-3 途径。本研究发现 MFSD7-ATP5I 与肿瘤的多形性增加和坏死减少有关。我们的功能获得和功能丧失实验证明 MFSD7-ATP5I 促进了肿瘤细胞的侵袭性。
