Small nucleolar RNA host gene 6 (SNHG6) is a newly discovered long non-coding RNA (lncRNA), while the regulatory mechanism of SNHG6 in chondrosarcoma is largely unknown. Here we found that SNHG6 expression was upregulated and showed positive correlation with the progression of chondrosarcoma. Functional assays demonstrated that SNHG6 was required for the proliferation, migration, and invasion of chondrosarcoma cells. Mechanistic study revealed that SNHG6 could recruit EZH2 and maintain high level of H3K27me3 to repress the transcription of tumor-suppressor genes, including KLF6. KLF6 was found to bind to the promoter region of SP1 and restrained its transcription, while SP1 could be recruited to the promoter region of SNHG6 and promoted its transcription to form a positive loop. In summary, this study reveals that SP1-induced SNHG6 forms a positive loop to facilitate the carcinogenesis of chondrosarcoma through the suppression of KLF6 by recruiting EZH2, which manifests the oncogenic function of SNHG6 in chondrosarcoma.

小核仁RNA宿主基因6（SNHG6）是一种新发现的长链非编码RNA（lncRNA），而SNHG6在软骨肉瘤中的调控机制很大程度上未知。在这里我们发现SNHG6表达上调并与软骨肉瘤的进展呈正相关。功能分析表明，SNHG6 是软骨肉瘤细胞增殖、迁移和侵袭所必需的。机制研究表明，SNHG6 可以招募 EZH2 并维持高水平的 H3K27me3 来抑制肿瘤抑制基因（包括 KLF6）的转录。研究发现KLF6与SP1的启动子区域结合并抑制其转录，而SP1可以被招募到SNHG6的启动子区域并促进其转录形成正环。综上所述，本研究揭示SP1诱导的SNHG6通过招募EZH2抑制KLF6形成正环，促进软骨肉瘤的癌变，体现了SNHG6在软骨肉瘤中的致癌功能。