Department of General Surgery, The Affiliated Jianhu Hospital of Nantong University, Jianhu People's Hospital, Jianhu, Jiangsu Province China.
Department of Operating Room, The Affiliated Jianhu Hospital of Nantong University, Jianhu People's Hospital, Jianhu, Jiangsu Province, China.
Bioengineered. 2021 Dec;12(1):7446-7458. doi: 10.1080/21655979.2021.1975969.
Hepatocellular carcinoma (HCC) is considered as a common malignancy worldwide. Considerable evidence has illustrated that abnormally expressed long noncoding RNAs (lncRNAs) are in a close correlation with the initiation and progression of various tumors, including HCC. LncRNA small nucleolar RNA host gene 22 (SNHG22) has been reported to play important roles in tumor initiation, but its role and mechanism are little known in HCC. In our report, we discovered the high level of SNHG22 in HCC tissues and cells, and the high expression of SNHG22 was correlated with unfavorable clinical outcome in HCC patients. Functional assays implied that SNHG22 deficiency suppressed cell proliferation, migration, invasion, and angiogenesis in vitro. Additionally, it was also confirmed that silenced SNHG22 suppressed tumor growth and angiogenesis in vivo. Mechanistic exploration revealed that SNHG22 recruited DNMT1 to miR-16-5p DNA promoter through EZH2 and inhibited miR-16-5p transcription via DNA methylation. Finally, we verified that the suppression of miR-16-5p countervailed the suppressive effect of SNHG22 deficiency on HCC cell proliferation, migration, invasion, and angiogenesis. Conclusively, this study clarified the SNHG22/EZH2/DNMT1/miR-16-5p axis and revealed that SNHG22 could be an underlying biomarker for HCC.
肝细胞癌（HCC）被认为是一种常见的全球恶性肿瘤。大量证据表明，异常表达的长非编码 RNA（lncRNA）与各种肿瘤的发生和发展密切相关，包括 HCC。据报道，lncRNA 小核仁 RNA 宿主基因 22（SNHG22）在肿瘤发生中起重要作用，但在 HCC 中其作用和机制知之甚少。在我们的报告中，我们发现 SNHG22 在 HCC 组织和细胞中高表达，并且 SNHG22 的高表达与 HCC 患者的不良临床结局相关。功能分析表明，SNHG22 缺失抑制了 HCC 细胞的增殖、迁移、侵袭和血管生成。此外，还证实沉默 SNHG22 抑制了体内肿瘤生长和血管生成。机制探索表明，SNHG22 通过 EZH2 将 DNMT1 募集到 miR-16-5p 的 DNA 启动子，通过 DNA 甲基化抑制 miR-16-5p 的转录。最后，我们验证了 miR-16-5p 的抑制作用抵消了 SNHG22 缺失对 HCC 细胞增殖、迁移、侵袭和血管生成的抑制作用。总之，本研究阐明了 SNHG22/EZH2/DNMT1/miR-16-5p 轴，并表明 SNHG22 可能是 HCC 的潜在生物标志物。
