Down regulation of human positive coactivator 4 suppress tumorigenesis and lung metastasis of osteosarcoma

Abstract

Osteosarcoma is a kind of primary malignant bone tumor with the highest incidence and an extraordinarily poor prognosis and early pulmonary metastasis formation as a frequent occurrence. Transcriptional positive coactivator 4 (PC4) has multiple functions in DNA replication, transcription, repair and chromatin organization, even in tumorigenesis. However, the precise function of PC4 in osteosarcoma is still unclear and controversial. In this paper we found PC4 was upregulated in patient-derived osteosarcoma tissues compared to normal. Moreover, higher expression of PC4 was correlated with poorer overall survival and advanced clinicopathological tumor staging. Down regulation of PC4 in the highly metastatic osteosarcoma cells reduced the malignant behaviors in vitro and in vivo. Analyzing the downstream genes affected obviously by shPC4 with RNA sequencing, we found knocking down PC4 will inhibit the propensity for lung metastasis through transcriptional suppression of MMPs pathways. Taken together, PC4 may be an attractive therapeutic strategy for osteosarcoma, especially in preventing lung metastasis formation.