CCT6A is associated with CDC20, Enneking stage and prognosis in osteosarcoma, and its knockdown suppresses osteosarcoma cell viability and invasion

Abstract

Chaperonin-containing tailless complex polypeptide 1 subunit 6A (CCT6A) regulates the proliferation, invasiveness and stemness of numerous types of cancer, and may interact with cell division cycle 20 (CDC20); however, its implication in osteosarcoma remains unclear. The present study aimed to investigate the relationship between CCT6A and CDC20, and their association with clinical features and prognosis. Subsequently, the present study explored the effects of their knockdown on osteosarcoma cell malignant behaviors. A total of 52 patients with osteosarcoma underwent tumor resection were retrospectively analyzed. CCT6A and CDC20 expression levels in tumor and nontumor tissues were detected by reverse transcription-quantitative PCR and immunohistochemistry. In addition, CCT6A and CDC20 small interfering RNA molecules were transfected into osteosarcoma cell lines. The results revealed that the mRNA (P<0.001) and protein (P<0.001) expression levels of CCT6A were elevated in tumor tissues compared with those in nontumor tissues. Tumor CCT6A mRNA expression was correlated with elevated CDC20 mRNA expression (P<0.001), higher Enneking stage (P=0.039), abnormal lactate dehydrogenase (LDH) level (>300 U/l) (P=0.048), lower pathological response (P=0.024) and worse disease-free survival (DFS) (P=0.015). Tumor CCT6A protein expression was also associated with increased CDC20 protein (P<0.001), elevated Enneking stage (P=0.005), abnormal LDH (P=0.019), decreased pathological response (P=0.014), shorter DFS (P=0.030) and overall survival (OS) (P=0.027). After adjustment by multivariate Cox analyses, tumor CCT6A mRNA expression was shown to independently predict lower pathological response (P=0.033) and poor DFS (P=0.028), but not OS. Regarding CDC20, it was associated with a higher Enneking stage and lower pathological response (both P<0.05), whereas it failed to estimate DFS or OS.In vitro experiments demonstrated that CCT6A and CDC20 knockdown inhibited proliferation and invasion, and enhanced apoptosis in U-2 OS and Saos-2 cells (all P<0.05). In conclusion, CCT6A is associated with CDC20, Enneking stage and prognosis of osteosarcoma, and its knockdown decreases the viability and invasion of osteosarcoma cells.