Department of Stomatology, The First People's Hospital of Yongkang, Yongkang, Zhejiang, China.
Bioengineered. 2022 Apr;13(4):9425-9434. doi: 10.1080/21655979.2022.2060452.
Emerging evidence has demonstrated that long noncoding RNA (lncRNAs) play a vital role in the development of head and neck squamous cell carcinoma (HNSCC); however, the biological effects and underlying mechanisms of human leukocyte antigen complex group-18 HCG18 (HCG18) have not yet been reported in HNSCC. In this study, we detected the expression of the HCG18 in HNSCC cell lines and patient tissues. We observed that HCG18 was upregulated in HNSCC patient tissues and cell lines. Furthermore, silencing of HCG18 significantly inhibited proliferation, migration, and invasion of HNSCC cells, whereas the opposite effects were detected in the HCG18-overexpressed group. We also found that HCG18 directly binds to the functional protein cyclin D1. Upregulated cyclin D1 reversed the inhibitory effects of HCG18 in HNSCC cell lines and activated the WNT pathway-related proteins (AXIN2, survivin, c-Myc, and β-catenin) simultaneously. Knockdown of cyclin D1 could accelerate the inhibitory effects of HCG18 and decrease the expression of AXIN2, survivin, c-Myc, and β-catenin. This indicated that lncRNA HCG18 might be involved in the tumorigenesis of HNSCC via the cyclin D1-WNT pathway. These results suggest that lncRNA HCG18 could act as a promising prognostic biomarker and potential therapeutic target in HNSCC patients.
已有研究表明，长链非编码 RNA（lncRNA）在头颈部鳞状细胞癌（HNSCC）的发生发展中发挥着重要作用；然而，人类白细胞抗原复合体 18 组HCG18（HCG18）在 HNSCC 中的生物学作用及其潜在机制尚未见报道。在本研究中，我们检测了 HCG18 在 HNSCC 细胞系和患者组织中的表达情况。结果发现，HCG18 在 HNSCC 患者组织和细胞系中呈高表达。此外，沉默 HCG18 可显著抑制 HNSCC 细胞的增殖、迁移和侵袭，而过表达 HCG18 则产生相反的作用。我们还发现，HCG18 可直接与功能蛋白 cyclin D1 结合。上调的 cyclin D1 逆转了 HCG18 在 HNSCC 细胞系中的抑制作用，同时激活了 WNT 通路相关蛋白（AXIN2、survivin、c-Myc 和β-catenin）。敲低 cyclin D1 可加速 HCG18 的抑制作用，降低 AXIN2、survivin、c-Myc 和β-catenin 的表达。这表明 lncRNA HCG18 可能通过 cyclin D1-WNT 通路参与 HNSCC 的发生发展。这些结果提示，lncRNA HCG18 可作为 HNSCC 患者有前途的预后标志物和潜在治疗靶点。
