长链非编码RNA XLOC_006786通过靶向miR-491-5p抑制NOTCH3信号通路,从而抑制骨肉瘤细胞的增殖、侵袭和转移。
Long noncoding RNA XLOC_006786 inhibits the proliferation, invasion and metastasis of osteosarcoma cells through NOTCH3 signaling pathway by targeting miR-491-5p.
发表日期:2023 Aug 13
作者:
Jia-Yi Xu, Yang-Fan Lv, Ya Cao, Hong-Min Ma, Xiang-Lin Hao, Lu Huang, Xue-Feng Tang, Qiao-Nan Guo
来源:
Cellular & Molecular Immunology
摘要:
最近的研究表明,长链非编码RNA(lncRNA)在许多疾病中尤其肿瘤中起着至关重要的作用。然而,lncRNA XLOC_006786(lncRNA-SPIDR-2:1)在恶性肿瘤,特别是人骨肉瘤中的确切作用尚不清楚。RT-qPCR、Western blotting、CCK-8检测和Transwell检测的结果显示,lncRNA XLOC_006786抑制了骨肉瘤细胞的增殖、侵袭和迁移,表明它可能是骨肉瘤中的一个肿瘤抑制基因。我们发现lncRNA XLOC_006786负调节了我们先前报道的骨肉瘤致癌基因NOTCH3。生物信息学分析显示,miR-491-5p可能是lncRNA XLOC_006786的直接靶标,而NOTCH3则是miR-491-5p的关键靶标。接着,我们验证了lncRNA XLOC_006786在体内可以防止肺转移性骨肉瘤的发生。综上所述,我们的研究表明,通过靶向miR-491-5p,lncRNA XLOC_006786通过NOTCH3信号通路抑制骨肉瘤的增殖、侵袭和转移。©2023.作者独家授权给日本人类细胞学会。
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.© 2023. The Author(s) under exclusive licence to Japan Human Cell Society.