青少年和儿童中最常见的原发性骨恶性肿瘤是骨肉瘤（OS）。目前标准治疗是手术和新辅助/手术后化疗的结合。虽然OS相关的化疗耐药性通常导致治疗药物效果差，但相关的分子相互作用仍然不清楚。本研究发现，长链非编码RNA（lncRNA）SNHG14在nutlin3a耐药OS细胞系NR-SJSA1中显著上调，并通过抑制铁死亡来促进治疗耐药性。在NR-SJSA1细胞中，LncRNA SNHG14的沉默导致药物耐受性的逆转和铁死亡的激活，而给予铁死亡抑制剂ferrostatin-1则消失。在机理上，lncRNA SNHG14靶向并下调miR-206的表达，进一步影响常见的铁死亡抑制剂SLC7A11，防止NR-SJSA1细胞进行铁死亡。综上所述，我们的发现强调了lncRNA SNHG14在NR-SJSA1细胞的铁死亡和治疗耐药性中的作用，因此为克服骨肉瘤细胞的耐药性和提高治疗效果提供了新的见解。©2022年。作者（们）独家授权施普林格自然美国公司使用。

The most prevalent form of primary osseous malignant tumor in adolescents and children is osteosarcoma (OS). A combination of surgery and neoadjuvant/post-surgery chemotherapy is currently the standard therapy. While the chemoresistance associated with OS generally leads to poor efficacy of therapeutic agents, the relevant molecular interaction is still elusive. Here, the lncRNA (long non-coding RNA) SNHG14 was found to be significantly upregulated in the nutlin3a-resistant OS cell line NR-SJSA1 and contributes to treatment resistance by suppressing ferroptosis. In NR-SJSA1 cells, knockdown of LncRNA SNHG14 resulted in a reversal of drug resistance and activation of ferroptosis, which disappeared when ferrostatin-1, a ferroptosis inhibitor, was added. Mechanistically, lncRNA SNHG14 targeted and down-regulated the expression of miR-206, further affecting the common ferroptosis inhibitor SLC7A11, and preventing NR-SJSA1 cells from undergoing ferroptosis. In conclusion, our findings highlight the involvement of lncRNA SNHG14 in ferroptosis and chemotherapy resistance of nutlin3a-resistant NR-SJSA1 cells, thus shedding new insight on how to overcome drug resistance in osteosarcoma cells and improve treatment efficacy.© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.