Huang Zhongming, Li Junhua, Du Shaohua, Tang Yanghua, Huang Ligang, Xiao Luwei, Tong Peijian
Department of Orthopaedic Surgery, Affiliated Jiangnan Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, China.
Department of Orthopaedic Surgery, Xiaoshan Chinese Medical Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, China.
Oncotarget. 2016 Jun 28;7(26):39872-39884. doi: 10.18632/oncotarget.9524.
The FK506-binding protein 14 (FKBP14) is a subfamily of immunophilins, has been implicated in various biochemical processes. However, its effects on the primary malignant bone tumor, osteosarcoma, are unclear. Here, we reported that FKBP14 may be an oncogene as it overexpressed in osteosarcoma tissues and cell lines, and FKBP14 expression was correlated with metastases, recurrence, tumor maximum diameter and poor survival time. FKBP14 was associated with the biological pathways including cell cycle, apoptosis and metastasis. Furthermore, we detected FKBP14 knockdown induced cell cycle arrest, apoptosis, invasion and adhesion in vitro. FKBP14 knockdown decreased the protein levels of PCNA, CDK1 and CCNB1 that promotes cell cycle, increased Bax, caspase-3 and caspase-7 protein involved in promoting cell apoptosis, and increased KIF4A expression as well as decreased SMC4 and TMEM33 proteins that contribute to cell invasion and adhesion. In addition, FKBP14 knockdown also caused a significant inhibition in tumor growth in vivo. Then, we found that the protein RhoA was identified as a binding partner of FKBP14. Taken together, FKBP14 may act as an oncogene in osteosarcoma via suppressing apoptosis and promoting invasion and adhesion in osteosarcoma carcinogenesis. FKBP14 may be a prognostic factor and potential target for osteosarcoma treatment.
FK506结合蛋白14（FKBP14）是亲免素的一个亚家族，参与多种生化过程。然而，其对原发性恶性骨肿瘤骨肉瘤的影响尚不清楚。在此，我们报告FKBP14可能是一种癌基因，因为它在骨肉瘤组织和细胞系中过表达，且FKBP14的表达与转移、复发、肿瘤最大直径及较差的生存时间相关。FKBP14与包括细胞周期、凋亡和转移在内的生物学途径相关。此外，我们检测到FKBP14基因敲低在体外可诱导细胞周期停滞、凋亡、侵袭和黏附。FKBP14基因敲低降低了促进细胞周期的PCNA、CDK1和CCNB1的蛋白水平，增加了参与促进细胞凋亡的Bax、caspase-3和caspase-7蛋白，并增加了KIF4A的表达，同时降低了有助于细胞侵袭和黏附的SMC4和TMEM33蛋白。此外，FKBP14基因敲低在体内也对肿瘤生长产生了显著抑制作用。然后，我们发现蛋白RhoA被确定为FKBP14的结合伴侣。综上所述，FKBP14可能通过抑制骨肉瘤细胞凋亡以及促进其侵袭和黏附，在骨肉瘤发生过程中发挥癌基因作用。FKBP14可能是骨肉瘤的一个预后因素和潜在的治疗靶点。
