Qu Zhigang, Li Shenglong
Department of Spine Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
Department of Bone and Soft Tissue Tumor Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning, China.
J Cell Physiol. 2020 Jan 29. doi: 10.1002/jcp.29582.
As one of the most aggressive malignancies, osteosarcoma has high risks of death. Although long noncoding RNAs (lncRNAs) may promote the osteosarcoma progression as verified, the potential molecular mechanism of lncRNAs in osteosarcoma remains unknown. Herein, we analyzed lncRNA microarray of osteosarcoma and selected LINC01278 as the study object. Then, we found that the expression of LINC01278 tested by quantitative reverse-transcription polymerase chain reaction was enhanced in tumor tissues compared with the para-carcinoma tissues and related to clinical stage, distant metastasis in osteosarcoma. In addition, the clinical outcomes were poor in osteosarcoma patients with high LINC01278 level. Moreover, LINC01278 promoted proliferation and restrained apoptosis in osteosarcoma cells. Afterward, mechanistic studies turned out that LINC01278 was a competing endogenous RNA of parathyroid hormone type 1 receptor (PTHR1) in osteosarcoma by sponging miR-133a-3p, which was considered as a tumor inhibitor in osteosarcoma. Furthermore, PTHR1 downregulation restored the impacts of inhibited miR-133a-3p on the processes in osteosarcoma cells. Our findings clarified that the carcinogenic effect of LINC01278 in osteosarcoma was mediated through miR-133a-3p/PTHR1 signaling, creating a novel insight into good targets for the therapy and prognosis of osteosarcoma.
作为最具侵袭性的恶性肿瘤之一,骨肉瘤具有很高的死亡风险。尽管长链非编码RNA(lncRNAs)已被证实可能促进骨肉瘤进展,但其在骨肉瘤中的潜在分子机制仍不清楚。在此,我们分析了骨肉瘤的lncRNA芯片,并选择LINC01278作为研究对象。然后,我们发现通过定量逆转录聚合酶链反应检测的LINC01278在肿瘤组织中的表达与癌旁组织相比有所增强,且与骨肉瘤的临床分期、远处转移相关。此外,LINC01278水平高的骨肉瘤患者临床预后较差。而且,LINC01278促进骨肉瘤细胞增殖并抑制其凋亡。随后,机制研究表明,在骨肉瘤中,LINC01278通过海绵吸附miR-133a-3p作为甲状旁腺激素1型受体(PTHR1)的竞争性内源性RNA,而miR-133a-3p被认为是骨肉瘤中的一种肿瘤抑制因子。此外,PTHR1的下调恢复了抑制miR-133a-3p对骨肉瘤细胞进程的影响。我们的研究结果表明,LINC01278在骨肉瘤中的致癌作用是通过miR-133a-3p/PTHR1信号介导的,为骨肉瘤的治疗和预后提供了新的良好靶点见解。