Department of Spinal Surgery, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen 518110, Guangdong, China.
Department of Quality Control, Affiliated Longhua Central Hospital, Guangdong Medical University, Shenzhen 518110, Guangdong, China.
Biomed Pharmacother. 2018 Oct;106:850-857. doi: 10.1016/j.biopha.2018.07.003. Epub 2018 Jul 11.
The long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) overexpression was found in various tumors and the dysregulated expression of SNHG12 contributed to multidrug resistance in non-small cell lung cancer. However, the role of SNHG12 in doxorubicin resistance of osteosarcoma is still unclear. In present study, we explored the function and underlying mechanism of SNHG12 on doxorubicin resistance in osteosarcoma. High expression of SNHG12 was associated with doxorubicin resistance and a poor overall survival in osteosarcoma. Furthermore, doxorubicin-resistant cells revealed a higher expression of SNHG12 compared with doxorubicin-sensitive cells. Moreover, dual luciferase reporter and RNA immunoprecipitation assays revealed that miR-320a targeted to SNHG12. Besides, knockdown of SNHG12 contributed to the upregulation of miR-320a and improved the sensitivity of doxorubicin. Additionally, miR-320a inhibited the expression of Myeloid cell leukemia 1 (MCL1). Finally, the results indicated that SNHG12 mediated doxorubicin resistance of osteosarcoma via miR-320a/MCL1 axis.
长链非编码 RNA 小核仁 RNA 宿主基因 12（SNHG12）在各种肿瘤中过表达，SNHG12 的表达失调导致非小细胞肺癌的多药耐药。然而，SNHG12 在骨肉瘤中对阿霉素耐药的作用仍不清楚。在本研究中，我们探讨了 SNHG12 对骨肉瘤中阿霉素耐药的作用及其潜在机制。SNHG12 的高表达与骨肉瘤的阿霉素耐药和整体生存不良相关。此外，与阿霉素敏感细胞相比，阿霉素耐药细胞中 SNHG12 的表达更高。此外，双荧光素酶报告和 RNA 免疫沉淀实验表明，miR-320a 靶向 SNHG12。此外，敲低 SNHG12 可上调 miR-320a 并提高阿霉素的敏感性。此外，miR-320a 抑制髓系细胞白血病 1（MCL1）的表达。最后，结果表明 SNHG12 通过 miR-320a/MCL1 轴介导骨肉瘤的阿霉素耐药。
