Tesser-Gamba Francine, Lopes Luana Joyce da Silva, Petrilli Antonio Sergio, Toledo Silvia Regina Caminada
Department of Pediatrics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Federal University of São Paulo, São Paulo-SP, Brazil.
Department of Morphology and Genetics, Genetics Laboratory, Pediatric Oncology Institute (IOP/GRAACC), Federal University of São Paulo, São Paulo-SP, Brazil.
Mol Carcinog. 2016 Nov;55(11):1700-1713. doi: 10.1002/mc.22420. Epub 2015 Oct 13.
Osteosarcomas (OS) are the most common malignant bone tumors, and the identification of useful tumor biomarkers and target proteins is required to predict the clinical outcome of patients and therapeutic response as well as to develop novel therapeutic strategies. In our previous study, MAPK7 has been identified as a candidate oncogene, and a promising prognostic marker for OS. Sequential activation of protein kinases within the mitogen-activated protein kinase (MAPK) cascades is a common mechanism of signal transduction in many cellular processes. In this study, we investigated the behavior of MAPK7 gene in OS cell lines. Technical viability, proliferation, migration, invasion, and apoptosis were used to evaluate the function of the MAPK7 gene. We evaluated the behavior of the OS cells with MAPK7 gene silenced, not silenced, and exposed to the main chemotherapy drugs used in OS treatment. We found that silenced MAPK7 gene is effective at suppressing cell proliferation, inhibiting cell migration, and invasion. Furthermore, MAPK7 is an important activator of transcription factors and is the main expression modulator of other key genes in the MAPK pathway. In summary, our study suggests that MAPK7 might be a promising therapeutic target for OS. © 2015 Wiley Periodicals, Inc.
骨肉瘤(OS)是最常见的恶性骨肿瘤,需要鉴定有用的肿瘤生物标志物和靶蛋白,以预测患者的临床结果和治疗反应,并制定新的治疗策略。在我们之前的研究中,MAPK7已被鉴定为候选癌基因,是骨肉瘤一个有前景的预后标志物。丝裂原活化蛋白激酶(MAPK)级联反应中蛋白激酶的顺序激活是许多细胞过程中信号转导的常见机制。在本研究中,我们研究了骨肉瘤细胞系中MAPK7基因的行为。通过技术可行性、增殖、迁移、侵袭和凋亡来评估MAPK7基因的功能。我们评估了MAPK7基因沉默、未沉默以及暴露于骨肉瘤治疗中使用的主要化疗药物的骨肉瘤细胞的行为。我们发现沉默的MAPK7基因在抑制细胞增殖、抑制细胞迁移和侵袭方面有效。此外,MAPK7是转录因子的重要激活剂,是MAPK途径中其他关键基因的主要表达调节因子。总之,我们的研究表明MAPK7可能是骨肉瘤一个有前景的治疗靶点。© 2015威利期刊公司