Long non-coding RNA tumor suppressor candidate 7 functions as a tumor suppressor and inhibits proliferation in osteosarcoma
Long non-coding RNA tumor suppressor candidate 7 functions as a tumor suppressor and inhibits proliferation in osteosarcoma
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DOI：
10.1007/s13277-015-4414-y
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发表时间：
2016-07-01
期刊：
影响因子：
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通讯作者：
Li, Zhenzhong
中科院分区：
文献类型：
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作者：
Cong, Menglin;Li, Jianmin;Li, Zhenzhong
骨肉瘤是最常见的骨恶性肿瘤。近年来的研究表明，长链非编码RNA（longnoncodingRNAs，lncRNA）在肿瘤的发生、发展中起着重要作用。然而，很少有lncRNA在骨肉瘤中被研究。在此，我们报道了一种新的lncRNA，肿瘤抑制因子候选物7（TUSC 7），与成对的非肿瘤组织相比，在骨肉瘤组织中显著下调，并且TUSC 7的低表达表明骨肉瘤患者的生存率低（HR = 0.313，95%置信区间（CI）0.092-0.867）。进一步分析发现，TUSC 7拷贝数的丢失与TUSC 7的低表达相关，此外，TUSC 7拷贝数的丢失也提示骨肉瘤患者预后不良（HR = 3.994，95%CI 1.147-13.91）。利用两种骨肉瘤细胞系HOS和MG 63研究TUSC 7的生物学功能。CCK-8法检测发现，TUSC 7基因沉默后，细胞增殖能力增强，殖民地形成能力增强。进一步的结果表明，si-TUSC 7处理对细胞周期没有影响，而凋亡细胞的百分比下降。Western blot结果显示，TUSC 7基因沉默后，Bcl 2蛋白表达下调。最后，我们用MG 63细胞建立了裸鼠移植瘤模型。与阴性对照组相比，TUSC 7基因沉默组在体内肿瘤生长明显增强。因此，我们证明了TUSC 7可能是骨肉瘤中潜在的肿瘤抑制因子。
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.