长链非编码 RNA HOTAIR/miRNA-206 海绵调控 STC2，并进一步影响头颈部鳞状细胞癌的细胞生物学功能。

Long non-coding RNA HOTAIR/microRNA-206 sponge regulates STC2 and further influences cell biological functions in head and neck squamous cell carcinoma.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, Peking University First Hospital, Beijing, China.

Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

出版信息

Cell Prolif. 2019 Sep;52(5):e12651. doi: 10.1111/cpr.12651. Epub 2019 Jul 11.

OBJECTIVE

It is essential to characterize underlying molecular mechanism associated with head and neck squamous cell carcinoma (HNSCC) and identify promising therapeutic targets. Herein, we explored role of homeobox transcript antisense RNA (HOTAIR) in HNSCC to regulate stanniocalcin-2 (STC2) by sponging microRNA-206 (miR-206).

METHODS

HNSCC-related differentially expressed genes and regulation network amongst HOTAIR, miR-206 and STC2 were identified. Next, effect of HOTAIR on cell biological functions of HNSCC was identified after transfection of cells with HOTAIR overexpressed plasmids or siRNA against HOTAIR. PI3K/AKT signalling pathway-related gene expression was measured after miR-206 and STC2 were suppressed. Cell invasion, migration and proliferation were assessed. Finally, tumour growth was assessed to determine the effects of HOTAIR/miR-206/STC2 axis in vivo.

RESULTS

HOTAIR specifically bound to miR-206 and miR-206 targeted STC2. Downregulated HOTAIR or upregulated miR-206 suppressed HNSCC cell proliferation, invasion and migration. miR-206 inhibited PI3K/AKT signalling pathway by down-regulating STC2. Besides, silenced HOTAIR or overexpressed miR-206 repressed the tumour growth of nude mice with HNSCC.

CONCLUSION

HOTAIR regulated HNSCC cell biological functions by binding to miR-206 through STC2.

目的

阐明与头颈部鳞状细胞癌（HNSCC）相关的潜在分子机制，并鉴定有前途的治疗靶点是至关重要的。本研究旨在探讨反义转录物 HOX 基因座转录物（HOTAIR）在 HNSCC 中的作用，通过海绵吸附 microRNA-206（miR-206）来调节 STC2。

方法

鉴定了与 HNSCC 相关的差异表达基因以及 HOTAIR、miR-206 和 STC2 之间的调控网络。然后，通过转染 HOTAIR 过表达质粒或针对 HOTAIR 的 siRNA，鉴定 HOTAIR 对 HNSCC 细胞生物学功能的影响。抑制 miR-206 和 STC2 后，测量 PI3K/AKT 信号通路相关基因的表达。评估细胞侵袭、迁移和增殖。最后，评估肿瘤生长以确定 HOTAIR/miR-206/STC2 轴在体内的作用。

结果

HOTAIR 特异性结合 miR-206，miR-206 靶向 STC2。下调 HOTAIR 或上调 miR-206 抑制 HNSCC 细胞的增殖、侵袭和迁移。miR-206 通过下调 STC2 抑制 PI3K/AKT 信号通路。此外，沉默 HOTAIR 或过表达 miR-206 抑制了携带 HNSCC 的裸鼠的肿瘤生长。