Wang Xin, Yu Yan, He Yuting, Cai Qiqing, Gao Songtao, Yao Weitao, Liu Zhiyong, Tian Zhichao, Han Qicai, Wang Weiwei, Sun Ranran, Luo Yonggang, Li Chao
Department of Bone and Soft Tissue, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Oncotarget. 2017 Dec 20;9(2):2502-2514. doi: 10.18632/oncotarget.23506. eCollection 2018 Jan 5.
Osteosarcoma (OS) is the most common primary malignant bone tumor in childhood and adolescence with poor prognosis. The mechanism underlying tumorigenesis and development of OS is largely unknown. ALDH1B1 has been reported to involve in many kinds of human cancers and functions as an oncogene, but the role of ALDH1B1 in OS has not been investigated comprehensively. In the present study, we aimed to examine clinical value and biological function of ALDH1B1 in OS. Firstly, we investigated the roles of ALDH1B1 on an OS tissue microarray (TMA) as well as two OS cohorts from GEO database. We found that ALDH1B1 was significantly up-regulated in OS tissues and was independently associated with poor prognosis. Moreover, ALDH1B1 silencing could suppress the proliferation, migration, invasion and inhibit the growth of xenograft tumor and of OS cells . Additional, ALDH1B1 knockdown increased the apoptosis rate and lead to cell cycle arrest in G1 stage of OS cell . More importantly, the inhibition of ALDH1B1 expression could increase the sensitivity of OS cells to chemotherapy, which suggested that ALDH1B1 might be served as a therapeutic target to reverse drug resistance in chemotherapy in OS patients. Taken together, our founding suggested that ALDH1B1 contributes to OS tumor progression and drug resistance, which may represent a novel prognostic marker and potential therapeutic target for OS patients.
骨肉瘤(OS)是儿童和青少年中最常见的原发性恶性骨肿瘤,预后较差。骨肉瘤发生和发展的潜在机制在很大程度上尚不清楚。据报道,醛脱氢酶1B1(ALDH1B1)参与多种人类癌症,并作为一种癌基因发挥作用,但ALDH1B1在骨肉瘤中的作用尚未得到全面研究。在本研究中,我们旨在探讨ALDH1B1在骨肉瘤中的临床价值和生物学功能。首先,我们在一个骨肉瘤组织芯片(TMA)以及来自基因表达综合数据库(GEO)的两个骨肉瘤队列中研究了ALDH1B1的作用。我们发现,ALDH1B1在骨肉瘤组织中显著上调,并且与预后不良独立相关。此外,沉默ALDH1B1可以抑制骨肉瘤细胞的增殖、迁移、侵袭,并抑制异种移植肿瘤和骨肉瘤细胞的生长。另外,敲低ALDH1B1可增加骨肉瘤细胞的凋亡率,并导致细胞周期停滞在G1期。更重要的是,抑制ALDH1B1的表达可以增加骨肉瘤细胞对化疗的敏感性,这表明ALDH1B1可能作为一个治疗靶点来逆转骨肉瘤患者化疗中的耐药性。综上所述,我们的研究结果表明,ALDH1B1促进骨肉瘤的肿瘤进展和耐药性,这可能代表骨肉瘤患者一种新的预后标志物和潜在的治疗靶点。