Maternal embryonic leucine zipper kinase serves as a poor prognosis marker and therapeutic target in osteosarcoma

Oncol Rep. 2020 Sep;44(3):1037-1048. doi: 10.3892/or.2020.7686. Epub 2020 Jul 13.

Salim F A Jeddo ^# 1, Xianfu Wei ^# 1, Ka Li ¹, Xin Li ¹, Qiang Yang ¹, Samina Dongol ², Jianmin Li ¹

• PMID: 32705239
• PMCID: PMC7388486
• DOI: 10.3892/or.2020.7686

Abstract

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.

Keywords: osteosarcoma; maternal embryonic lucine zipper kinase; MELK inhibitor OTSSP167; oncogene; prognostic marker.

#BioGems; #Annexin V APC Apoptosis Detection Kit