Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma
复制标题
母体胚胎亮氨酸拉链激酶作为骨肉瘤的不良预后标志物和治疗靶点
DOI：
10.3892/or.2020.7686
复制
发表时间：
2020-09-01
期刊：
影响因子：
4.2
通讯作者：
Li, Jianmin
中科院分区：
文献类型：
--
作者：
Jeddo, Salim F. A.;Wei, Xianfu;Li, Jianmin
骨肉瘤是最常见的原发性骨恶性肿瘤，常影响儿童和青少年。由于疾病的侵袭性以及化疗耐药的风险，治疗骨肉瘤存在一些挑战。目前正在进行大量的研究，目的是确定这种恶性肿瘤的预后和治疗标志物。母胚亮氨酸拉链激酶（MELK）是近年来在几种癌症中被研究的致癌基因。本研究检测了MELK在骨肉瘤和正常组织样本中的表达情况，并通过CCK-8、创面愈合、迁移侵袭和细胞凋亡等实验验证了MELK表达对骨肉瘤细胞增殖、转移、细胞周期和细胞凋亡的影响。确定MELK在骨肉瘤癌症进展中的作用，揭示MELK表达与骨肉瘤预后之间的关联。结果表明，敲低MELK可导致细胞体外增殖、迁移和侵袭能力降低，并增强细胞凋亡和细胞周期阻滞。此外，我们还评估了靶向MELK抑制剂OTSSP167在体外和体内对骨肉瘤肿瘤进展的影响。从机制上看，MELK通过PI3K/Akt/mTOR信号通路调节PCNA和MMP9的表达，促进骨肉瘤的增殖和转移。因此，本研究揭示了MELK的致癌作用，并确立了MELK作为骨肉瘤预后和治疗的有价值的标志物。
Osteosarcoma is the most common primary malignancy of bones and frequently affects young children and adolescents. There are several challenges associated with treating osteosarcoma owing to the aggressiveness of the disease, as well as the risk of chemoresistance. Numerous studies are being performed with the aim of identifying improved prognostic and therapeutic markers for this malignancy. Maternal embryonic leucine zipper kinase (MELK) is an oncogene that has been studied in several types of cancer in recent years. In the present study, the expression of MELK in osteosarcoma and normal tissue samples was examined, and the effects of MELK expression on osteosarcoma cellular proliferation, metastasis, the cell cycle and apoptosis were demonstrated using CCK-8, wound healing, migration and invasion and apoptosis assays. The role of MELK in cancer progression in osteosarcoma was determined, revealing the association between MELK expression and prognosis of osteosarcoma. It was demonstrated that knockdown of MELK resulted in reduced proliferation, migration and invasion in vitro along with potentiation of apoptosis and cell cycle arrest. Furthermore, the effect of the targeted MELK inhibitor, OTSSP167, on tumor progression of osteosarcoma in vitro and in vivo was assessed. Mechanistically, it was demonstrated that MELK promoted osteosarcoma proliferation and metastasis by regulating PCNA and MMP9 expression via the PI3K/Akt/mTOR signaling pathway. Thus, the present study revealed the oncogenic role played by MELK, and established MELK as a valuable prognostic and therapeutic marker in osteosarcoma.