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长链非编码RNA肿瘤抑制候选物7作为一种肿瘤抑制因子发挥作用,并抑制骨肉瘤的增殖。

Long non-coding RNA tumor suppressor candidate 7 functions as a tumor suppressor and inhibits proliferation in osteosarcoma.

作者信息

Cong Menglin, Li Jianmin, Jing Rui, Li Zhenzhong

机构信息

Department of Orthopedic Surgery, Shandong University School of Medicine, Jinan, China.

Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Jinan, China.

出版信息

Tumour Biol. 2016 Jul;37(7):9441-50. doi: 10.1007/s13277-015-4414-y. Epub 2016 Jan 19.

DOI:10.1007/s13277-015-4414-y
PMID:26781978
Abstract

Osteosarcoma is the most common malignant tumor of bone. Recent studies have proven long non-coding RNAs (lncRNAs) play important roles in the tumorigenesis and progression of cancer. However, few lncRNAs have been investigated in osteosarcoma. Here, we reported a novel lncRNA, tumor suppressor candidate 7 (TUSC7), was significantly downregulated in osteosarcoma tissues compared with paired non-tumor tissues and low expression of TUSC7 indicated poor survival (HR = 0.313, 95 % confidence interval (CI) 0.092-0.867) of osteosarcoma patients. Further analysis revealed that loss copy number of TUSC7 was correlated with low expression of TUSC7, and additionally, loss of TUSC7 copy number also indicated poor prognosis (HR = 3.994, 95 % CI 1.147-13.91) of osteosarcoma patients. Two osteosarcoma cell lines, HOS and MG63, were utilized to investigate biological function of TUSC7. Cell counting kit 8 (CCK-8) assay revealed that after silence of TUSC7, cell proliferation ability increased and the colony formation ability also increased. Further results showed that cell cycle was not affected by treatment of si-TUSC7, while the percentage of apoptotic cells decreased. Western blot showed that after silence of TUSC7, the proapoptotic Bcl2 expression was downregulated. Finally, we established xenograft tumor models in nude mice with MG63 cells. Compared with negative control group, silence of TUSC7 significantly promoted tumor growth in vivo. Thus, we demonstrated that TUSC7 could be a potential tumor suppressor in osteosarcoma.

摘要

骨肉瘤是最常见的骨恶性肿瘤。最近的研究证明长链非编码RNA(lncRNA)在肿瘤的发生和发展中发挥重要作用。然而,在骨肉瘤中很少有lncRNA被研究。在此,我们报告了一种新的lncRNA,肿瘤抑制候选因子7(TUSC7),与配对的非肿瘤组织相比,其在骨肉瘤组织中显著下调,并且TUSC7低表达提示骨肉瘤患者生存较差(风险比[HR]=0.313,95%置信区间[CI]为0.092 - 0.867)。进一步分析显示,TUSC7的拷贝数缺失与TUSC7低表达相关,此外,TUSC7拷贝数缺失也提示骨肉瘤患者预后较差(HR = 3.994,95%CI为1.147 - 13.91)。利用两种骨肉瘤细胞系HOS和MG63研究TUSC7的生物学功能。细胞计数试剂盒8(CCK - 8)检测显示,TUSC7沉默后,细胞增殖能力增强,集落形成能力也增强。进一步结果表明,si - TUSC7处理未影响细胞周期,但凋亡细胞百分比降低。蛋白质免疫印迹法显示,TUSC7沉默后,促凋亡蛋白Bcl2表达下调。最后,我们用MG63细胞在裸鼠中建立了异种移植瘤模型。与阴性对照组相比,TUSC7沉默显著促进了体内肿瘤生长。因此,我们证明TUSC7可能是骨肉瘤中一种潜在的肿瘤抑制因子。

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