Tian Zhoubin, Yang Guang, Jiang Peng, Zhang Laibo, Wang Jian, Sun Shui
Pharmazie. 2017 Sep 1;72(9):537-542. doi: 10.1691/ph.2017.7548.
Osteosarcoma is a bone tumor without effective treatment in the world. Recently, long non-coding RNAs (lncRNAs) are considered as essential regulators in cancer progression. LncSox4 plays crucial roles in liver tumor-initiating cells self-renewal and tumor initiation. However, the effect of lncSox4 in osteosarcoma remains largely unclear. Quantitative real-time PCR (qRT-PCR) and Northern blot were performed to detect lncSox4 expressions in osteosarcoma. The functions of lncSox4 in osteosarcoma were determined using cell viability and migration assays. In addition, the proteins associated with lncSox4 were further evaluated by western blot. We found that lncSox4 was expressed highly in U-20S and Mg63 cells and osteosarcoma tumor tissues (all P < 0.001). LncSox4 silencing attenuated but lncSox4 overexpression promoted cell viability (all P < 0.001) and migration (P < 0.01) in the Mg63 cells. Next, we found lncSox4 regulation of osteosarcoma is involved in β-catenin, and overexpression of lncSox4 could stable β-catenin expression. Further, Wnt agonist CID11210285 completely abolished the decrease of Mg63 cells viability induced by lncSox4 silencing when cells cultured for 3 and 4 days (both P < 0.01), while Wnt inhibitor IWP-3 abolished the increase of Mg63 cells viability induced by overexpression of lncSox4 after treatment for 2 (P < 0.01), 3 (P < 0.001) and 4 (P < 0.01) days. Our study offers evidence for the first time that lncSox4 plays a positive role in osteosarcoma development and progression, and could act as a potential prognostic and therapy biomarker.
骨肉瘤是一种在全球范围内都没有有效治疗方法的骨肿瘤。最近，长链非编码RNA（lncRNAs）被认为是癌症进展中的关键调节因子。LncSox4在肝肿瘤起始细胞的自我更新和肿瘤发生中起关键作用。然而，lncSox4在骨肉瘤中的作用仍 largely不清楚。进行了定量实时PCR（qRT-PCR）和Northern印迹以检测骨肉瘤中lncSox4的表达。使用细胞活力和迁移试验确定lncSox4在骨肉瘤中的功能。此外，通过蛋白质印迹进一步评估与lncSox4相关的蛋白质。我们发现lncSox4在U-20S和Mg63细胞以及骨肉瘤肿瘤组织中高表达（所有P < 0.001）。lncSox4沉默减弱，但lncSox4过表达促进Mg63细胞的活力（所有P < 0.001）和迁移（P < 0.01）。接下来，我们发现lncSox4对骨肉瘤的调节涉及β-连环蛋白，并且lncSox4的过表达可以稳定β-连环蛋白的表达。此外，当细胞培养3天和4天时，Wnt激动剂CID11210285完全消除了lncSox4沉默诱导的Mg63细胞活力的降低（两者P < 0.01），而Wnt抑制剂IWP-3在处理2天（P < 0.01），3天（P < 0.001）和4天（P < 0.01）后消除了lncSox4过表达诱导的Mg63细胞活力的增加。我们的研究首次提供证据表明lncSox4在骨肉瘤的发生和发展中起积极作用，并且可以作为潜在的预后和治疗生物标志物。
