PSKH1 affects proliferation and invasion of osteosarcoma cells via the p38/MAPK signaling pathway

Abstract

Malignant osteosarcoma (OS) is a tumor of bone and soft tissue that metastasizes early and has a high mortality rate. Protein serine kinase H1 (PSKH1), an autophosphorylating human protein serine kinase, controls the trafficking of serine/arginine-rich domain, with downstream effects on mRNA processing. It is also associated with tumor progression. However, how this protein contributes to OS progression and metastasis is unknown. The present study evaluated the potential effect of PSKH1 on proliferation of human OS cells. OS cell lines were used in Cell Counting Kit-8, colony formation, wound-healing and Transwell assays, to investigate cellular processes such as proliferation, migration and invasion and underlying molecular mechanisms. Expression of PSKH1 in OS tissue was significantly greater than in adjacent non-malignant tissue. PSKH1 knockdown inhibited the proliferation, migration and invasion of OS cells. Conversely, PSKH1 overexpression promoted proliferation of OS cells. PSKH1 upregulated phosphorylated-p38 in OS cells. Moreover, the p38 MAPK inhibitor SB203580 effectively blocked the tumor-promoting action of PSKH1. Furthermore, PSKH1 knockdown inhibited tumor growth and metastasis in vivo. In conclusion, these findings suggested that PSKH1 promoted OS proliferation, migration and invasion. Thus, PSKH1 may serve an oncogenic role in the development of human OS.

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

“…β‐Phenylethyl isothiocyanate induces the proliferation of human OS cells by changing iron metabolism, disrupting redox homeostasis, and activating the MAPK pathway. p38 phosphorylation in OS cells is upregulated by PSKH1, and p38 overexpression promotes the proliferation of OS cells 200 …”

“…In both in vivo and in vitro models, TF3 triggers cellular iron death and apoptosis by activating the ROS and MAPK signaling pathways, reducing glutathione depletion, promoting the accumulation of reactive oxygen species (ROS), and enhancing the Fenton response‐induced oxidative response 245 . Additionally, the p38 MAPK inhibitor SB203580 effectively blocks the protumorigenic effect of PSKH1 200 …”

“…p38 phosphorylation in OS cells is upregulated by PSKH1, and p38 overexpression promotes the proliferation of OS cells. 200 …”

“… 245 Additionally, the p38 MAPK inhibitor SB203580 effectively blocks the protumorigenic effect of PSKH1. 200 …”