Xu Jia-Yi, Lv Yang-Fan, Cao Ya, Ma Hong-Min, Hao Xiang-Lin, Huang Lu, Tang Xue-Feng, Guo Qiao-Nan
Department of Pathology, Xinqiao Hospital, Army Medical University, Chongqing, China.
Hum Cell. 2023 Nov;36(6):2140-2151. doi: 10.1007/s13577-023-00958-8. Epub 2023 Aug 13.
Recent research has indicated that Long noncoding RNAs (LncRNAs) are crucial in many disorders, especially tumors. However, the exact role of LncRNA XLOC_006786 (LncRNA-SPIDR-2:1) in malignancies, especially in human osteosarcoma, is unclear. The results of RT‒qPCR, western blotting, CCK-8 assays, and Transwell assays showed that LncRNA XLOC_006786 inhibited osteosarcoma cell proliferation, invasion, and migration, indicating that it may be a tumor suppressor gene in osteosarcoma. We found that LncRNA XLOC_006786 negatively regulated NOTCH3, which is an oncogenic gene in osteosarcoma, as we previously reported. Bioinformatics analysis showed that miR-491-5p may be a direct target of LncRNA XLOC_006786, while NOTCH3 is a key target of miR-491-5p. Then, we verified that LncRNA XLOC_006786 could prevent lung metastatic osteosarcoma in vivo. Taken together, our research showed that LncRNA XLOC_006786 suppresses osteosarcoma proliferation, invasion, and metastasis through the NOTCH3 signaling pathway by targeting miR-491-5p.
最近的研究表明，长链非编码RNA（lncRNAs）在许多疾病尤其是肿瘤中起着关键作用。然而，lncRNA XLOC_006786（lncRNA-SPIDR-2:1）在恶性肿瘤尤其是人类骨肉瘤中的具体作用尚不清楚。逆转录定量聚合酶链反应（RT-qPCR）、蛋白质免疫印迹法、细胞计数试剂盒-8（CCK-8）检测和Transwell检测结果表明，lncRNA XLOC_006786抑制骨肉瘤细胞的增殖、侵袭和迁移，表明它可能是骨肉瘤中的一个肿瘤抑制基因。正如我们之前报道的，我们发现lncRNA XLOC_006786负向调节NOTCH3，NOTCH3是骨肉瘤中的一个致癌基因。生物信息学分析表明，miR-491-5p可能是lncRNA XLOC_006786的直接靶点，而NOTCH3是miR-491-5p的关键靶点。然后，我们证实lncRNA XLOC_006786在体内可预防骨肉瘤肺转移。综上所述，我们的研究表明，lncRNA XLOC_006786通过靶向miR-491-5p，经由NOTCH3信号通路抑制骨肉瘤的增殖、侵袭和转移。
