Wang Ning, Chen Yong, Wu Jie
Department of Orthopedics, Center Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.
Department of Hand Surgery, Center Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning 110024, P.R. China.
Oncol Lett. 2023 Apr 4;25(5):201. doi: 10.3892/ol.2023.13787. eCollection 2023 May.
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. 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.
含伴侣蛋白的无尾复合多肽1亚基6A(CCT6A)调节多种类型癌症的增殖、侵袭性和干性,并且可能与细胞分裂周期20(CDC20)相互作用;然而,其在骨肉瘤中的作用仍不清楚。本研究旨在探讨CCT6A与CDC20之间的关系,以及它们与临床特征和预后的关联。随后,本研究探究了敲低它们对骨肉瘤细胞恶性行为的影响。对52例行肿瘤切除术的骨肉瘤患者进行回顾性分析。通过逆转录定量PCR和免疫组织化学检测肿瘤组织和非肿瘤组织中CCT6A和CDC20的表达水平。此外,将CCT6A和CDC20小干扰RNA分子转染到骨肉瘤细胞系中。结果显示,与非肿瘤组织相比,肿瘤组织中CCT6A的mRNA(P<0.001)和蛋白(P<0.001)表达水平升高。肿瘤CCT6A mRNA表达与CDC20 mRNA表达升高(P<0.001)、Enneking分期较高(P=0.039)、乳酸脱氢酶(LDH)水平异常(>300 U/l)(P=0.048)、病理反应较低(P=0.024)和无病生存期(DFS)较差(P=0.015)相关。肿瘤CCT6A蛋白表达也与CDC20蛋白增加(P<0.001)、Enneking分期升高(P=0.005)、LDH异常(P=0.019)、病理反应降低(P=0.014)、DFS缩短(P=0.030)和总生存期(OS)(P=0.027)相关。经多变量Cox分析调整后,肿瘤CCT6A mRNA表达显示可独立预测较低的病理反应(P=0.033)和较差的DFS(P=0.028),但不能预测OS。关于CDC20,它与较高的Enneking分期和较低的病理反应相关(均P<0.05),而它无法评估DFS或OS。实验表明,敲低CCT6A和CDC20可抑制U-2 OS和Saos-2细胞的增殖和侵袭,并增强其凋亡(均P<0.05)。总之,CCT6A与CDC20、Enneking分期及骨肉瘤预后相关,敲低CCT6A可降低骨肉瘤细胞的活力和侵袭性。